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Erschienen in: Seminars in Immunopathology 1/2019

09.07.2018 | Review

Cancer immune therapy for myeloid malignancies: present and future

verfasst von: Morten Orebo Holmström, Hans Carl Hasselbalch

Erschienen in: Seminars in Immunopathology | Ausgabe 1/2019

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Abstract

The myelodysplastic syndromes, the chronic myeloproliferative neoplasms, and the acute myeloid leukemia are malignancies of the myeloid hematopoietic stem cells of the bone marrow. The diseases are characterized by a dysregulation of the immune system as both the cytokine milieu, immune phenotype, immune regulation, and expression of genes related to immune cell functions are deregulated. Several treatment strategies try to circumvent this deregulation, and several clinical and preclinical trials have shown promising results, albeit not in the same scale as chimeric antigen receptor T cells have had in the treatment of refractory lymphoid malignancies. The use of immune checkpoint blocking antibodies especially in combination with hypomethylating agents has had some success—a success that will likely be enhanced by therapeutic cancer vaccination with tumor-specific antigens. In the chronic myeloproliferative neoplasms, the recent identification of immune responses against the Januskinase-2 and calreticulin exon 9 driver mutations could also be used in the vaccination setting to enhance the anti-tumor immune response. This immune response could probably be enhanced by the concurrent use of immune checkpoint inhibitors or by vaccination with epitopes from immune regulatory proteins such as arginase-1 and programmed death ligand-1. Herein, we provide an overview of current cancer immune therapeutic treatment strategies as well as potential future cancer immune therapeutic treatment options for the myeloid malignancies.
Literatur
1.
Zurück zum Zitat Vercauteren SM, Starczynowski DT, Sung S, McNeil K, Salski C, Jensen CL, Bruyere H, Lam WL, Karsan A (2012) T cells of patients with myelodysplastic syndrome are frequently derived from the malignant clone. Br J Haematol 156(3):409–412CrossRefPubMedPubMedCentral Vercauteren SM, Starczynowski DT, Sung S, McNeil K, Salski C, Jensen CL, Bruyere H, Lam WL, Karsan A (2012) T cells of patients with myelodysplastic syndrome are frequently derived from the malignant clone. Br J Haematol 156(3):409–412CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Larsen TS, Christensen JH, Hasselbalch HC, Pallisgaard N (2007) The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders. Br J Haematol 136:745–751CrossRefPubMed Larsen TS, Christensen JH, Hasselbalch HC, Pallisgaard N (2007) The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders. Br J Haematol 136:745–751CrossRefPubMed
3.
Zurück zum Zitat Kjaer L, Holmström MO, Cordua S, Andersen MH, Svane IM, Thomassen M, Kruse TA, Pallisgaard N, Skov V, Hasselbalch HC (2018) Sorted peripheral blood cells identify CALR mutations in B- and T-lymphocytes. Leuk Lymphoma 59:973–977CrossRefPubMed Kjaer L, Holmström MO, Cordua S, Andersen MH, Svane IM, Thomassen M, Kruse TA, Pallisgaard N, Skov V, Hasselbalch HC (2018) Sorted peripheral blood cells identify CALR mutations in B- and T-lymphocytes. Leuk Lymphoma 59:973–977CrossRefPubMed
4.
Zurück zum Zitat Dickinson AM, Norden J, Li S, Hromadnikova I, Schmid C et al (2017) Graft-versus-leukemia effect following hematopoietic stem cell transplantation for leukemia. Front Immunol 7:496CrossRef Dickinson AM, Norden J, Li S, Hromadnikova I, Schmid C et al (2017) Graft-versus-leukemia effect following hematopoietic stem cell transplantation for leukemia. Front Immunol 7:496CrossRef
5.
Zurück zum Zitat Le Dieu R, Taussig DC, Ramsay AG, Mitter R, Miraki-Moud F et al (2009) Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood 114:3909–3916CrossRefPubMedPubMedCentral Le Dieu R, Taussig DC, Ramsay AG, Mitter R, Miraki-Moud F et al (2009) Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood 114:3909–3916CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Schnorfeil FM, Lichtenegger FS, Emmerig K, Schlueter M, Neitz JS, Draenert R, Hiddemann W, Subklewe M (2015) T cells are functionally not impaired in AML: increased PD-1 expression is only seen at time of relapse and correlates with a shift towards the memory T cell compartment. J Hematol Oncol 8:93CrossRefPubMedPubMedCentral Schnorfeil FM, Lichtenegger FS, Emmerig K, Schlueter M, Neitz JS, Draenert R, Hiddemann W, Subklewe M (2015) T cells are functionally not impaired in AML: increased PD-1 expression is only seen at time of relapse and correlates with a shift towards the memory T cell compartment. J Hematol Oncol 8:93CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Jia B, Wang L, Claxton DF, Ehmann WC, Rybka WB, Mineishi S, Rizvi S, Shike H, Bayerl M, Schell TD, Hohl RJ, Zheng H (2018) Bone marrow CD8 T cells express high frequency of PD-1 and exhibit reduced anti-leukemia response in newly diagnosed AML patients. Blood Cancer J 8:34CrossRefPubMedPubMedCentral Jia B, Wang L, Claxton DF, Ehmann WC, Rybka WB, Mineishi S, Rizvi S, Shike H, Bayerl M, Schell TD, Hohl RJ, Zheng H (2018) Bone marrow CD8 T cells express high frequency of PD-1 and exhibit reduced anti-leukemia response in newly diagnosed AML patients. Blood Cancer J 8:34CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Szczepanski MJ, Szajnik M, Czystowska M, Mandapathil M, Strauss L, Welsh A, Foon KA, Whiteside TL, Boyiadzis M (2009) Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res 15:3325–3332CrossRefPubMedPubMedCentral Szczepanski MJ, Szajnik M, Czystowska M, Mandapathil M, Strauss L, Welsh A, Foon KA, Whiteside TL, Boyiadzis M (2009) Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res 15:3325–3332CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Shenghui Z, Yixiang H, Jianbo W, Kang Y, Laixi B, Yan Z, Xi X (2011) Elevated frequencies of CD4+CD25+CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. Int J Cancer 129:1373–1381CrossRefPubMed Shenghui Z, Yixiang H, Jianbo W, Kang Y, Laixi B, Yan Z, Xi X (2011) Elevated frequencies of CD4+CD25+CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. Int J Cancer 129:1373–1381CrossRefPubMed
10.
Zurück zum Zitat Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, Parmar S, Cortes J, Kantarjian H, Garcia-Manero G (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28:1280–1288CrossRefPubMed Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, Parmar S, Cortes J, Kantarjian H, Garcia-Manero G (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28:1280–1288CrossRefPubMed
11.
Zurück zum Zitat Ørskov AD, Treppendahl MB, Skovbo A, Holm MS, Friis LS et al (2015) Hypomethylation and up-regulation of PD-1in T cells by azacytidine in MDS/AML patients: a rationale for combined targeting of PD-1 and DNA methylation. Oncotarget 6:9612–9626CrossRefPubMedPubMedCentral Ørskov AD, Treppendahl MB, Skovbo A, Holm MS, Friis LS et al (2015) Hypomethylation and up-regulation of PD-1in T cells by azacytidine in MDS/AML patients: a rationale for combined targeting of PD-1 and DNA methylation. Oncotarget 6:9612–9626CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Kordasti SY, Ingram W, Hayden J, Darling D, Barber L, Afzali B, Lombardi G, Wlodarski MW, Maciejewski JP, Farzaneh F, Mufti GJ (2007) CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood 110:847–850CrossRefPubMed Kordasti SY, Ingram W, Hayden J, Darling D, Barber L, Afzali B, Lombardi G, Wlodarski MW, Maciejewski JP, Farzaneh F, Mufti GJ (2007) CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood 110:847–850CrossRefPubMed
13.
Zurück zum Zitat Chen X, E a E, Zhou J, Zhang L, Djeu J et al (2013) Induction of myelodysplasia by myeloid- derived suppressor cells. J Clin Invest 123:4595–4611CrossRefPubMedPubMedCentral Chen X, E a E, Zhou J, Zhang L, Djeu J et al (2013) Induction of myelodysplasia by myeloid- derived suppressor cells. J Clin Invest 123:4595–4611CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L et al (2013) Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood 122:749–758CrossRefPubMedPubMedCentral Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L et al (2013) Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood 122:749–758CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Chamuleau MED, Van De Loosdrecht AA, Hess CJ, Janssen JJWM, Zevenbergen A et al (2008) High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome. Haematologica 93:1894–1898CrossRefPubMed Chamuleau MED, Van De Loosdrecht AA, Hess CJ, Janssen JJWM, Zevenbergen A et al (2008) High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome. Haematologica 93:1894–1898CrossRefPubMed
16.
Zurück zum Zitat Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A et al (2006) Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood 109:2871–2878 Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A et al (2006) Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood 109:2871–2878
17.
Zurück zum Zitat Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC et al (2014) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:1–9CrossRef Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC et al (2014) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:1–9CrossRef
18.
Zurück zum Zitat Zeidan AM, Zeidner JF, Duffield A, Knaus HA, Ferguson A et al (2015) Stabilization of myelodysplastic syndromes (MDS) following hypomethylating agent (HMAs) failure using the immune checkpoint inhibitor Ipilimumab: a phase I trial. Blood 126:1666–1666 Zeidan AM, Zeidner JF, Duffield A, Knaus HA, Ferguson A et al (2015) Stabilization of myelodysplastic syndromes (MDS) following hypomethylating agent (HMAs) failure using the immune checkpoint inhibitor Ipilimumab: a phase I trial. Blood 126:1666–1666
20.
Zurück zum Zitat Daver N, Basu S, Garcia-Manero G, Cortes JE, Ravandi F et al (2017) Phase IB/II study of nivolumab with azacytidine (AZA) in patients (pts) with relapsed AML. J Clin Oncol 35:7026CrossRef Daver N, Basu S, Garcia-Manero G, Cortes JE, Ravandi F et al (2017) Phase IB/II study of nivolumab with azacytidine (AZA) in patients (pts) with relapsed AML. J Clin Oncol 35:7026CrossRef
21.
Zurück zum Zitat Vey N, Dumas P-Y, Recher C, Gastaud L, Lioure B et al (2017) Randomized phase 2 trial of lirilumab (anti-KIR monoclonal antibody, mAb) as maintenance treatment in elderly patients (pts) with acute myeloid leukemia (AML): results of the Effikir trial. Blood 130:889 Vey N, Dumas P-Y, Recher C, Gastaud L, Lioure B et al (2017) Randomized phase 2 trial of lirilumab (anti-KIR monoclonal antibody, mAb) as maintenance treatment in elderly patients (pts) with acute myeloid leukemia (AML): results of the Effikir trial. Blood 130:889
22.
Zurück zum Zitat Daver N, Boddu P, Guillermo G-M, Ravandi F, Jabbour E et al (2017) Phase IB/II study of lirilumab with azacytidine (AZA) in relapsed AML. Blood 130:2634 Daver N, Boddu P, Guillermo G-M, Ravandi F, Jabbour E et al (2017) Phase IB/II study of lirilumab with azacytidine (AZA) in relapsed AML. Blood 130:2634
23.
Zurück zum Zitat Qazilbash MH, Wieder E, Rios R, Lu S, Kant S et al (2004) Vaccination with the PR1 leukemia-associated antigen can induce complete remission in patients with myeloid leukemia. Blood 104:259 Qazilbash MH, Wieder E, Rios R, Lu S, Kant S et al (2004) Vaccination with the PR1 leukemia-associated antigen can induce complete remission in patients with myeloid leukemia. Blood 104:259
24.
Zurück zum Zitat Rezvani K, Yong ASM, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ (2008) Leukemia-associated antigen specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood 111:236–242CrossRefPubMedPubMedCentral Rezvani K, Yong ASM, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ (2008) Leukemia-associated antigen specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood 111:236–242CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C (2009) A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113:6541–6548CrossRefPubMed Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C (2009) A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113:6541–6548CrossRefPubMed
26.
Zurück zum Zitat Uttenthal B, Martinez-Davila I, Ivey A, Craddock C, Chen F, Virchis A, Kottaridis P, Grimwade D, Khwaja A, Stauss H, Morris EC (2014) Wilms’ tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia induces short-lived WT1-specific immune responses. Br J Haematol 164:366–375CrossRefPubMed Uttenthal B, Martinez-Davila I, Ivey A, Craddock C, Chen F, Virchis A, Kottaridis P, Grimwade D, Khwaja A, Stauss H, Morris EC (2014) Wilms’ tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia induces short-lived WT1-specific immune responses. Br J Haematol 164:366–375CrossRefPubMed
27.
Zurück zum Zitat Maslak PG, Dao T, Bernal Y, Chanel SM, Zhang R, Frattini M, Rosenblat T, Jurcic JG, Brentjens RJ, Arcila ME, Rampal R, Park JH, Douer D, Katz L, Sarlis N, Tallman MS, Scheinberg DA (2018) Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv 2:224–234CrossRefPubMedPubMedCentral Maslak PG, Dao T, Bernal Y, Chanel SM, Zhang R, Frattini M, Rosenblat T, Jurcic JG, Brentjens RJ, Arcila ME, Rampal R, Park JH, Douer D, Katz L, Sarlis N, Tallman MS, Scheinberg DA (2018) Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv 2:224–234CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Tsuboi A, Oka Y, Kyo T, Katayama Y, Elisseeva OA, Kawakami M, Nishida S, Morimoto S, Murao A, Nakajima H, Hosen N, Oji Y, Sugiyama H (2012) Long-term WT1 peptide vaccination for patients with acute myeloid leukemia with minimal residual disease. Leukemia 26:1410–1413CrossRefPubMed Tsuboi A, Oka Y, Kyo T, Katayama Y, Elisseeva OA, Kawakami M, Nishida S, Morimoto S, Murao A, Nakajima H, Hosen N, Oji Y, Sugiyama H (2012) Long-term WT1 peptide vaccination for patients with acute myeloid leukemia with minimal residual disease. Leukemia 26:1410–1413CrossRefPubMed
29.
Zurück zum Zitat Brayer J, Lancet JE, Powers J, List A, Balducci L, Komrokji R, Pinilla-Ibarz J (2015) WT1 vaccination in AML and MDS: a pilot trial with synthetic analog peptides. Am J Hematol 90:602–607CrossRefPubMedPubMedCentral Brayer J, Lancet JE, Powers J, List A, Balducci L, Komrokji R, Pinilla-Ibarz J (2015) WT1 vaccination in AML and MDS: a pilot trial with synthetic analog peptides. Am J Hematol 90:602–607CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Qazilbash MH, Wieder E, Thall PF, Wang X, Rios R, Lu S, Kanodia S, Ruisaard KE, Giralt SA, Estey EH, Cortes J, Komanduri KV, Clise-Dwyer K, Alatrash G, Ma Q, Champlin RE, Molldrem JJ (2017) PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31:697–704CrossRefPubMed Qazilbash MH, Wieder E, Thall PF, Wang X, Rios R, Lu S, Kanodia S, Ruisaard KE, Giralt SA, Estey EH, Cortes J, Komanduri KV, Clise-Dwyer K, Alatrash G, Ma Q, Champlin RE, Molldrem JJ (2017) PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31:697–704CrossRefPubMed
31.
Zurück zum Zitat Anguille S, Van De Velde AL, Smits EL, Van Tendeloo VF, Juliusson G et al (2017) Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood 130:1713–1721CrossRefPubMedPubMedCentral Anguille S, Van De Velde AL, Smits EL, Van Tendeloo VF, Juliusson G et al (2017) Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood 130:1713–1721CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Almstedt M, Blagitko-Dorfs N, Duque-Afonso J, Karbach J, Pfeifer D, Jäger E, Lübbert M (2010) The DNA demethylating agent 5-aza-2′-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res 34:899–905CrossRefPubMed Almstedt M, Blagitko-Dorfs N, Duque-Afonso J, Karbach J, Pfeifer D, Jäger E, Lübbert M (2010) The DNA demethylating agent 5-aza-2′-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res 34:899–905CrossRefPubMed
33.
Zurück zum Zitat Srivastava P, Paluch BE, Matsuzaki J, James SR, Collamat-Lai G, Blagitko-Dorfs N, Ford LA, Naqash R, Lübbert M, Karpf AR, Nemeth MJ, Griffiths EA (2016) Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy. Oncotarget 7:12840–12856CrossRefPubMedPubMedCentral Srivastava P, Paluch BE, Matsuzaki J, James SR, Collamat-Lai G, Blagitko-Dorfs N, Ford LA, Naqash R, Lübbert M, Karpf AR, Nemeth MJ, Griffiths EA (2016) Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy. Oncotarget 7:12840–12856CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Gang AO, Frøsig TM, Brimnes MK, Lyngaa R, Treppendahl MB, Grønbæk K, Dufva IH, Straten P, Hadrup SR (2014) 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies. Blood Cancer J. 4:e197CrossRefPubMedPubMedCentral Gang AO, Frøsig TM, Brimnes MK, Lyngaa R, Treppendahl MB, Grønbæk K, Dufva IH, Straten P, Hadrup SR (2014) 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies. Blood Cancer J. 4:e197CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Griffiths EA, Srivastava P, Matsuzaki J, Brumberger Z, Wang ES et al (2017) NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome. Clin Cancer Res 24:1019–1029CrossRefPubMedPubMedCentral Griffiths EA, Srivastava P, Matsuzaki J, Brumberger Z, Wang ES et al (2017) NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome. Clin Cancer Res 24:1019–1029CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Mehta RS, Chen X, Antony J, Boyiadzis M, Szabolcs P (2016) Generating peripheral blood derived lymphocytes reacting against autologous primary AML blasts. J Immunother 39:71–80CrossRefPubMedPubMedCentral Mehta RS, Chen X, Antony J, Boyiadzis M, Szabolcs P (2016) Generating peripheral blood derived lymphocytes reacting against autologous primary AML blasts. J Immunother 39:71–80CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Rosenblatt J, Stone RM, Uhl L, Neuberg D, Joyce R, Levine JD, Arnason J, McMasters M, Luptakova K, Jain S, Zwicker JI, Hamdan A, Boussiotis V, Steensma DP, DeAngelo DJ, Galinsky I, Dutt PS, Logan E, Bryant MP, Stroopinsky D, Werner L, Palmer K, Coll M, Washington A, Cole L, Kufe D, Avigan D (2016) Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions. Sci Transl Med 8:368ra171CrossRefPubMedPubMedCentral Rosenblatt J, Stone RM, Uhl L, Neuberg D, Joyce R, Levine JD, Arnason J, McMasters M, Luptakova K, Jain S, Zwicker JI, Hamdan A, Boussiotis V, Steensma DP, DeAngelo DJ, Galinsky I, Dutt PS, Logan E, Bryant MP, Stroopinsky D, Werner L, Palmer K, Coll M, Washington A, Cole L, Kufe D, Avigan D (2016) Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions. Sci Transl Med 8:368ra171CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, la Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci PG, Martelli MF, GIMEMA Acute Leukemia Working Party (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352:254–266CrossRefPubMed Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, la Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci PG, Martelli MF, GIMEMA Acute Leukemia Working Party (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352:254–266CrossRefPubMed
39.
Zurück zum Zitat Greiner J, Ono Y, Hofmann S, Schmitt A, Mehring E et al (2016) Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia. Blood 97:1282–1290 Greiner J, Ono Y, Hofmann S, Schmitt A, Mehring E et al (2016) Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia. Blood 97:1282–1290
40.
Zurück zum Zitat Greiner J, Schneider V, Schmitt M, Götz M, Döhner K et al (2013) Immune responses against the mutated region of cytoplasmatic NPM1 might contribute to the favorable clinical outcome of AML patients with NPM1 mutations (NPM1mut). Blood 122:1087–1088CrossRefPubMed Greiner J, Schneider V, Schmitt M, Götz M, Döhner K et al (2013) Immune responses against the mutated region of cytoplasmatic NPM1 might contribute to the favorable clinical outcome of AML patients with NPM1 mutations (NPM1mut). Blood 122:1087–1088CrossRefPubMed
41.
Zurück zum Zitat Kuželová K, Brodská B, Fuchs O, Dobrovolná M, Soukup P, Cetkovský P (2015) Altered HLA class I profile associated with type A/D nucleophosmin mutation points to possible anti-nucleophosmin immune response in acute myeloid leukemia. PLoS One 10:1–12CrossRef Kuželová K, Brodská B, Fuchs O, Dobrovolná M, Soukup P, Cetkovský P (2015) Altered HLA class I profile associated with type A/D nucleophosmin mutation points to possible anti-nucleophosmin immune response in acute myeloid leukemia. PLoS One 10:1–12CrossRef
42.
Zurück zum Zitat Greiner J, Hofmann S, Schmitt M, Götz M, Wiesneth M, Schrezenmeier H, Bunjes D, Döhner H, Bullinger L (2017) Acute myeloid leukemia with mutated nucleophosmin 1—an immunogenic AML subtype and potential candidate for immune checkpoint inhibition. Haematologica 102:e499–e501CrossRefPubMedPubMedCentral Greiner J, Hofmann S, Schmitt M, Götz M, Wiesneth M, Schrezenmeier H, Bunjes D, Döhner H, Bullinger L (2017) Acute myeloid leukemia with mutated nucleophosmin 1—an immunogenic AML subtype and potential candidate for immune checkpoint inhibition. Haematologica 102:e499–e501CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Scholl S, Salzmann S, Kaufmann A, Höffken K (2006) Flt3-ITD mutations can generate leukaemia specific neoepitopes: potential role for immunotherapeutic approaches. Leuk Lymphoma 47:307–312CrossRefPubMed Scholl S, Salzmann S, Kaufmann A, Höffken K (2006) Flt3-ITD mutations can generate leukaemia specific neoepitopes: potential role for immunotherapeutic approaches. Leuk Lymphoma 47:307–312CrossRefPubMed
44.
Zurück zum Zitat O’Hear C, Heiber JF, Schubert I, Fey G, Geiger TL (2015) Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. Haematologica 100:336–344CrossRefPubMedPubMedCentral O’Hear C, Heiber JF, Schubert I, Fey G, Geiger TL (2015) Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. Haematologica 100:336–344CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Mardiros A, Dos SC (2013) T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 122:3138–3148CrossRefPubMedPubMedCentral Mardiros A, Dos SC (2013) T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 122:3138–3148CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, Chen K, Shin M, Wall DM, Hönemann D, Gambell P, Westerman DA, Haurat J, Westwood JA, Scott AM, Kravets L, Dickinson M, Trapani JA, Smyth MJ, Darcy PK, Kershaw MH, Prince HM (2013) Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 21:2122–2129CrossRefPubMedPubMedCentral Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, Chen K, Shin M, Wall DM, Hönemann D, Gambell P, Westerman DA, Haurat J, Westwood JA, Scott AM, Kravets L, Dickinson M, Trapani JA, Smyth MJ, Darcy PK, Kershaw MH, Prince HM (2013) Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 21:2122–2129CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Hofmann S, Götz M, Scheider V, Guillaume P, Bunjes D et al (2013) Donor lymphocyte infusion induces polyspecific CD8+ T-cell responses with concurrent molecular remission in acute myeloid leukemia with NPM1 mutation. J Clin Oncol 31:2013–2015CrossRef Hofmann S, Götz M, Scheider V, Guillaume P, Bunjes D et al (2013) Donor lymphocyte infusion induces polyspecific CD8+ T-cell responses with concurrent molecular remission in acute myeloid leukemia with NPM1 mutation. J Clin Oncol 31:2013–2015CrossRef
48.
Zurück zum Zitat Lee JB, Minden MD, Chen WC, Streck E, Chen B et al (2017) Allogeneic human double negative T cells as a novel immunotherapy for acute myeloid leukemia and its underlying mechanisms. Clin Cancer Res 24:370–382CrossRefPubMedPubMedCentral Lee JB, Minden MD, Chen WC, Streck E, Chen B et al (2017) Allogeneic human double negative T cells as a novel immunotherapy for acute myeloid leukemia and its underlying mechanisms. Clin Cancer Res 24:370–382CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat Krupka C, Kufer P, Kischel R, Zugmaier G, Bögeholz J et al (2014) CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood 123:356–365CrossRefPubMed Krupka C, Kufer P, Kischel R, Zugmaier G, Bögeholz J et al (2014) CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood 123:356–365CrossRefPubMed
50.
Zurück zum Zitat Krupka C, Kufer P, Kischel R, Zugmaier G, Lichtenegger FS, Köhnke T, Vick B, Jeremias I, Metzeler KH, Altmann T, Schneider S, Fiegl M, Spiekermann K, Bauerle PA, Hiddemann W, Riethmüller G, Subklewe M (2016) Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism. Leukemia 30:484–491CrossRefPubMed Krupka C, Kufer P, Kischel R, Zugmaier G, Lichtenegger FS, Köhnke T, Vick B, Jeremias I, Metzeler KH, Altmann T, Schneider S, Fiegl M, Spiekermann K, Bauerle PA, Hiddemann W, Riethmüller G, Subklewe M (2016) Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism. Leukemia 30:484–491CrossRefPubMed
51.
Zurück zum Zitat Martner A, Rydström A, Riise RE, Aurelius J, Anderson H et al (2016) Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia. Oncoimmunology 5:1–11CrossRef Martner A, Rydström A, Riise RE, Aurelius J, Anderson H et al (2016) Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia. Oncoimmunology 5:1–11CrossRef
52.
Zurück zum Zitat Bernson E, Hallner A, Sander FE, Wilsson O, Werlenius O, Rydström A, Kiffin R, Brune M, Foà R, Aurelius J, Martner A, Hellstrand K, Thorén FB (2017) Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia. Leukemia 31:2552–2559CrossRefPubMedPubMedCentral Bernson E, Hallner A, Sander FE, Wilsson O, Werlenius O, Rydström A, Kiffin R, Brune M, Foà R, Aurelius J, Martner A, Hellstrand K, Thorén FB (2017) Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia. Leukemia 31:2552–2559CrossRefPubMedPubMedCentral
54.
Zurück zum Zitat Butt NM, Rojas JM, Wang L, Christmas SE, Abu-Eisha HM, Clark RE (2005) Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects. Haematologica 90:1315–1323PubMed Butt NM, Rojas JM, Wang L, Christmas SE, Abu-Eisha HM, Clark RE (2005) Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects. Haematologica 90:1315–1323PubMed
55.
Zurück zum Zitat Rusakiewicz S, Madrigal A, Travers P, Dodi AI (2009) BCR/ABL-specific CD8+ T cells can be detected from CML patients, but are only expanded from healthy donors. Cancer Immunol Immunother 58:1449–1457CrossRefPubMed Rusakiewicz S, Madrigal A, Travers P, Dodi AI (2009) BCR/ABL-specific CD8+ T cells can be detected from CML patients, but are only expanded from healthy donors. Cancer Immunol Immunother 58:1449–1457CrossRefPubMed
56.
Zurück zum Zitat Berke Z, Andersen MH, Pedersen M, Fugger L, Zeuthen J, Haurum JS (2000) Peptides spanning the junctional region of both the abl/bcr and the bcr/abl fusion proteins bind common HLA class I molecules. Leukemia 14:419–426CrossRefPubMed Berke Z, Andersen MH, Pedersen M, Fugger L, Zeuthen J, Haurum JS (2000) Peptides spanning the junctional region of both the abl/bcr and the bcr/abl fusion proteins bind common HLA class I molecules. Leukemia 14:419–426CrossRefPubMed
57.
Zurück zum Zitat Posthuma EF, Falkenburg JH, Apperley JF, Gratwohl A, Roosnek E et al (1999) HLA-B8 and HLA-A3 coexpressed with HLA-B8 are associated with a reduced risk of the development of chronic myeloid leukemia. Blood 93:3863–3865PubMed Posthuma EF, Falkenburg JH, Apperley JF, Gratwohl A, Roosnek E et al (1999) HLA-B8 and HLA-A3 coexpressed with HLA-B8 are associated with a reduced risk of the development of chronic myeloid leukemia. Blood 93:3863–3865PubMed
58.
Zurück zum Zitat Pinilla-Ibarz J, Cathcart K, Korontsvit T, Soignet S, Bocchia M, Caggiano J, Lai L, Jimenez J, Kolitz J, Scheinberg DA (2000) Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood 95:1781–1787PubMed Pinilla-Ibarz J, Cathcart K, Korontsvit T, Soignet S, Bocchia M, Caggiano J, Lai L, Jimenez J, Kolitz J, Scheinberg DA (2000) Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood 95:1781–1787PubMed
59.
Zurück zum Zitat Brauer KM, Werth D, Von Schwarzenberg K, Bringmann A, Kanz L et al (2007) BCR-ABL activity is critical for the immunogenicity of chronic myelogenous leukemia cells. Cancer Res 67:5489–5497CrossRefPubMed Brauer KM, Werth D, Von Schwarzenberg K, Bringmann A, Kanz L et al (2007) BCR-ABL activity is critical for the immunogenicity of chronic myelogenous leukemia cells. Cancer Res 67:5489–5497CrossRefPubMed
60.
Zurück zum Zitat Bocchia M, Defina M, Aprile L, Ippoliti M, Crupi R, Rondoni M, Gozzetti A, Lauria F (2010) Complete molecular response in CML after p210 BCR-ABL1-derived peptide vaccination. Nat Rev Clin Oncol 7:600–603CrossRefPubMed Bocchia M, Defina M, Aprile L, Ippoliti M, Crupi R, Rondoni M, Gozzetti A, Lauria F (2010) Complete molecular response in CML after p210 BCR-ABL1-derived peptide vaccination. Nat Rev Clin Oncol 7:600–603CrossRefPubMed
61.
Zurück zum Zitat Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJP, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D’Andrea A, Fröhling S, Döhner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397CrossRefPubMed Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJP, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D’Andrea A, Fröhling S, Döhner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397CrossRefPubMed
62.
Zurück zum Zitat Kralovics R, Passamonti F, Buser AAS, Teo S-SS-S, Tiedt R et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790CrossRefPubMed Kralovics R, Passamonti F, Buser AAS, Teo S-SS-S, Tiedt R et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790CrossRefPubMed
63.
Zurück zum Zitat Verstovsek S, R a M, Gotlib J, Levy RS, Gupta V et al (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366:799–807CrossRefPubMedPubMedCentral Verstovsek S, R a M, Gotlib J, Levy RS, Gupta V et al (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366:799–807CrossRefPubMedPubMedCentral
64.
Zurück zum Zitat Cervantes F, Pereira A (2017) Does ruxolitinib prolong the survival of patients with myelofibrosis? Blood 129:832–838CrossRefPubMed Cervantes F, Pereira A (2017) Does ruxolitinib prolong the survival of patients with myelofibrosis? Blood 129:832–838CrossRefPubMed
65.
Zurück zum Zitat Marti-Carvajal AJ, Anand V, Sola I (2015) Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis. Cochrane Database Syst Rev 4:CD010298 Marti-Carvajal AJ, Anand V, Sola I (2015) Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis. Cochrane Database Syst Rev 4:CD010298
66.
Zurück zum Zitat Pourcelot E, Trocme C, Mondet J, Bailly S, Toussaint B, Mossuz P (2014) Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications. Exp Hematol 42:360–368CrossRefPubMed Pourcelot E, Trocme C, Mondet J, Bailly S, Toussaint B, Mossuz P (2014) Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications. Exp Hematol 42:360–368CrossRefPubMed
67.
Zurück zum Zitat Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A (2011) Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 29:1356–1363CrossRefPubMed Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A (2011) Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 29:1356–1363CrossRefPubMed
68.
Zurück zum Zitat Bjørn ME, Andersen CL, Jensen MK, Hasselbalch HC (2014) Circulating YKL-40 in myelofibrosis a potential novel biomarker of disease activity and the inflammatory state. Eur J Haematol 93:224–228CrossRefPubMed Bjørn ME, Andersen CL, Jensen MK, Hasselbalch HC (2014) Circulating YKL-40 in myelofibrosis a potential novel biomarker of disease activity and the inflammatory state. Eur J Haematol 93:224–228CrossRefPubMed
69.
Zurück zum Zitat Rameshwar P, Denny TN, Stein D, Gascón P, Rameshwar P et al (1994) Monocyte adhesion in patients with bone marrow fibrosis is required for the production of fibrogenic cytokines. Potential role for interleukin-1 and TGF-beta. J Immunol 153:2819–2830PubMed Rameshwar P, Denny TN, Stein D, Gascón P, Rameshwar P et al (1994) Monocyte adhesion in patients with bone marrow fibrosis is required for the production of fibrogenic cytokines. Potential role for interleukin-1 and TGF-beta. J Immunol 153:2819–2830PubMed
70.
Zurück zum Zitat Skov V, Riley CH, Thomassen M, Larsen TS, Jensen MK, Bjerrum OW, Kruse TA, Hasselbalch HC (2013) Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis. Leuk Lymphoma 54:2269–2273CrossRefPubMed Skov V, Riley CH, Thomassen M, Larsen TS, Jensen MK, Bjerrum OW, Kruse TA, Hasselbalch HC (2013) Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis. Leuk Lymphoma 54:2269–2273CrossRefPubMed
71.
Zurück zum Zitat Skov V, Larsen TS, Thomassen M, Riley CH, Jensen MK, Bjerrum OW, Kruse TA, Hasselbalch HC (2012) Molecular profiling of peripheral blood cells from patients with polycythemia vera and related neoplasms: identification of deregulated genes of significance for inflammation and immune surveillance. Leuk Res 36:1387–1392CrossRefPubMed Skov V, Larsen TS, Thomassen M, Riley CH, Jensen MK, Bjerrum OW, Kruse TA, Hasselbalch HC (2012) Molecular profiling of peripheral blood cells from patients with polycythemia vera and related neoplasms: identification of deregulated genes of significance for inflammation and immune surveillance. Leuk Res 36:1387–1392CrossRefPubMed
72.
Zurück zum Zitat Wang JC, Kundra A, Andrei M, Baptiste S, Chen C, Wong C (2016) Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm. Leuk Res 43:39–43CrossRefPubMed Wang JC, Kundra A, Andrei M, Baptiste S, Chen C, Wong C (2016) Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm. Leuk Res 43:39–43CrossRefPubMed
73.
Zurück zum Zitat Prestipino A, Emhardt AJ, Aumann K, Sullivan DO’, Gorantla SP et al (2018) Oncogenic JAK2 V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med 10:1–13CrossRef Prestipino A, Emhardt AJ, Aumann K, Sullivan DO’, Gorantla SP et al (2018) Oncogenic JAK2 V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med 10:1–13CrossRef
74.
Zurück zum Zitat Riley CH, Jensen MK, Brimnes MK, Hasselbalch HC, Bjerrum OW, Straten P, Svane IM (2011) Increase in circulating CD4+CD25+Foxp3+ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α. Blood 118:2170–2173CrossRefPubMed Riley CH, Jensen MK, Brimnes MK, Hasselbalch HC, Bjerrum OW, Straten P, Svane IM (2011) Increase in circulating CD4+CD25+Foxp3+ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α. Blood 118:2170–2173CrossRefPubMed
75.
Zurück zum Zitat Silver RT, Kiladjian J-J, Hasselbalch HC (2013) Interferon and the treatment of polycythemia vera, essential thrombocytemia and myelofibrosis. Exp Hematol 6:1–10CrossRef Silver RT, Kiladjian J-J, Hasselbalch HC (2013) Interferon and the treatment of polycythemia vera, essential thrombocytemia and myelofibrosis. Exp Hematol 6:1–10CrossRef
76.
Zurück zum Zitat Kovacsovics-Bankowski M, Kelley TW, Efimova O, Kim SJ, Wilson A, Swierczek S, Prchal J (2015) Changes in peripheral blood lymphocytes in polycythemia vera and essential thrombocythemia patients treated with pegylated-interferon alpha and correlation with JAK2 V617F allelic burden. Exp Hematol Oncol 5:28CrossRefPubMed Kovacsovics-Bankowski M, Kelley TW, Efimova O, Kim SJ, Wilson A, Swierczek S, Prchal J (2015) Changes in peripheral blood lymphocytes in polycythemia vera and essential thrombocythemia patients treated with pegylated-interferon alpha and correlation with JAK2 V617F allelic burden. Exp Hematol Oncol 5:28CrossRefPubMed
77.
Zurück zum Zitat Riley CH, Brimnes MK, Hansen M, Jensen MK, Hasselbalch HC, Kjaer L, Straten P, Svane IM (2016) Interferon-α induces marked alterations in circulating regulatory T cells, NK cell subsets, and dendritic cells in patients with JAK2V617F-positive essential thrombocythemia and polycythemia vera. Eur J Haematol 97:83–92CrossRefPubMed Riley CH, Brimnes MK, Hansen M, Jensen MK, Hasselbalch HC, Kjaer L, Straten P, Svane IM (2016) Interferon-α induces marked alterations in circulating regulatory T cells, NK cell subsets, and dendritic cells in patients with JAK2V617F-positive essential thrombocythemia and polycythemia vera. Eur J Haematol 97:83–92CrossRefPubMed
78.
Zurück zum Zitat Riley CH, Hansen M, Brimnes MK, Hasselbalch HC, Bjerrum OW, Straten P, Svane IM, Jensen MK (2015) Expansion of circulating CD56(bright) natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α. Eur J Haematol 94:227–234CrossRefPubMed Riley CH, Hansen M, Brimnes MK, Hasselbalch HC, Bjerrum OW, Straten P, Svane IM, Jensen MK (2015) Expansion of circulating CD56(bright) natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α. Eur J Haematol 94:227–234CrossRefPubMed
79.
Zurück zum Zitat Skov V, Riley CH, Thomassen M, Kjær L, Stauffer Larsen T, Bjerrum OW, Kruse TA, Hasselbalch HC (2017) The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms. Leuk Lymphoma 58:1914–1921CrossRefPubMed Skov V, Riley CH, Thomassen M, Kjær L, Stauffer Larsen T, Bjerrum OW, Kruse TA, Hasselbalch HC (2017) The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms. Leuk Lymphoma 58:1914–1921CrossRefPubMed
80.
Zurück zum Zitat Kiladjian J-J, Giraudier S, Cassinat B (2015) Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone. Leukemia 30:1–6 Kiladjian J-J, Giraudier S, Cassinat B (2015) Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone. Leukemia 30:1–6
81.
Zurück zum Zitat Xiong Z, Yan Y, Liu E, Silver RT, Verstovsek S, Yang F, Wang H, Prchal J, Yang XF (2007) Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera. Clin Immunol 122:279–287CrossRefPubMed Xiong Z, Yan Y, Liu E, Silver RT, Verstovsek S, Yang F, Wang H, Prchal J, Yang XF (2007) Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera. Clin Immunol 122:279–287CrossRefPubMed
82.
Zurück zum Zitat Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, du MQ, Greaves M, Bowen D, Huntly BJP, Harrison CN, Cross NCP, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR (2013) Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369:2391–2405CrossRefPubMedPubMedCentral Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, du MQ, Greaves M, Bowen D, Huntly BJP, Harrison CN, Cross NCP, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR (2013) Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369:2391–2405CrossRefPubMedPubMedCentral
83.
Zurück zum Zitat Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NCC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schönegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369:2379–2390CrossRefPubMed Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NCC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schönegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369:2379–2390CrossRefPubMed
84.
Zurück zum Zitat Holmstrom MO, Hjortso MD, Ahmad SM, Met O, Martinenaite E et al (2017) The JAK2V617F mutation is a target for specific T-cells in the JAK2V617F positive myeloproliferative neoplasms. Leukemia 31:495–498CrossRefPubMed Holmstrom MO, Hjortso MD, Ahmad SM, Met O, Martinenaite E et al (2017) The JAK2V617F mutation is a target for specific T-cells in the JAK2V617F positive myeloproliferative neoplasms. Leukemia 31:495–498CrossRefPubMed
85.
Zurück zum Zitat Holmstrom MO, Riley CH, Svane IM, Hasselbalch HC, Andersen MH et al (2016) The CALR exon 9 mutations are shared neoantigens in patients with CALR mutant chronic myeloproliferative neoplasms. Leukemia 30:2413–2416CrossRefPubMed Holmstrom MO, Riley CH, Svane IM, Hasselbalch HC, Andersen MH et al (2016) The CALR exon 9 mutations are shared neoantigens in patients with CALR mutant chronic myeloproliferative neoplasms. Leukemia 30:2413–2416CrossRefPubMed
86.
Zurück zum Zitat Holmstrom MO, Martinenaite E, Ahmad SM, Met O, Friese C et al (2018) The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy. Leukemia 32:429–437CrossRefPubMed Holmstrom MO, Martinenaite E, Ahmad SM, Met O, Friese C et al (2018) The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy. Leukemia 32:429–437CrossRefPubMed
87.
Zurück zum Zitat Araki M, Yang Y, Masubuchi N, Hironaka Y, Takei H, Morishita S, Mizukami Y, Kan S, Shirane S, Edahiro Y, Sunami Y, Ohsaka A, Komatsu N (2016) Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. Blood 127:1307–1316CrossRefPubMed Araki M, Yang Y, Masubuchi N, Hironaka Y, Takei H, Morishita S, Mizukami Y, Kan S, Shirane S, Edahiro Y, Sunami Y, Ohsaka A, Komatsu N (2016) Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. Blood 127:1307–1316CrossRefPubMed
88.
Zurück zum Zitat Melief CJM, van der Burg SH (2008) Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8:351–360CrossRefPubMed Melief CJM, van der Burg SH (2008) Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8:351–360CrossRefPubMed
89.
Zurück zum Zitat Anguille S, Lion E, Willemen Y, Van Tendeloo VFI, Berneman ZN, Smits ELJM (2011) Interferon-α in acute myeloid leukemia: an old drug revisited. Leukemia 25:739–748CrossRefPubMed Anguille S, Lion E, Willemen Y, Van Tendeloo VFI, Berneman ZN, Smits ELJM (2011) Interferon-α in acute myeloid leukemia: an old drug revisited. Leukemia 25:739–748CrossRefPubMed
90.
Zurück zum Zitat Munir S, Larsen SK, Iversen TZ, Donia M, Klausen TW, Svane IM, Straten P, Andersen MH (2012) Natural CD4 + T-cell responses against indoleamine 2,3-dioxygenase. PLoS One 7:e34568CrossRefPubMedPubMedCentral Munir S, Larsen SK, Iversen TZ, Donia M, Klausen TW, Svane IM, Straten P, Andersen MH (2012) Natural CD4 + T-cell responses against indoleamine 2,3-dioxygenase. PLoS One 7:e34568CrossRefPubMedPubMedCentral
91.
Zurück zum Zitat Munir S, Andersen GH, Met Ö, Donia M, Frøsig TM et al (2013) HLA-restricted CTL that are specific for the immune checkpoint ligand PD-L1 occur with high frequency in cancer patients. Cancer Res 73:1764–1776CrossRefPubMed Munir S, Andersen GH, Met Ö, Donia M, Frøsig TM et al (2013) HLA-restricted CTL that are specific for the immune checkpoint ligand PD-L1 occur with high frequency in cancer patients. Cancer Res 73:1764–1776CrossRefPubMed
92.
Zurück zum Zitat Martinenaite E, Mortensen REJ, Hansen M, Orebo Holmström M, Munir Ahmad S et al (2017) Frequent adaptive immune responses against arginase-1. Oncoimmunology:e1404215 Martinenaite E, Mortensen REJ, Hansen M, Orebo Holmström M, Munir Ahmad S et al (2017) Frequent adaptive immune responses against arginase-1. Oncoimmunology:e1404215
93.
Zurück zum Zitat Munir Ahmad S, Martinenaite E, Hansen M, Junker N, Borch TH, Met Ö, Donia M, Svane IM, Andersen MH (2016) PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine. Oncoimmunology. 5:e1202391CrossRefPubMedPubMedCentral Munir Ahmad S, Martinenaite E, Hansen M, Junker N, Borch TH, Met Ö, Donia M, Svane IM, Andersen MH (2016) PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine. Oncoimmunology. 5:e1202391CrossRefPubMedPubMedCentral
94.
Zurück zum Zitat Ahmad SM, Larsen SK, Svane IM, Andersen MH (2014) Harnessing PD-L1-specific cytotoxic T cells for anti-leukemia immunotherapy to defeat mechanisms of immune escape mediated by the PD-1 pathway. Leukemia 28:236–238CrossRefPubMed Ahmad SM, Larsen SK, Svane IM, Andersen MH (2014) Harnessing PD-L1-specific cytotoxic T cells for anti-leukemia immunotherapy to defeat mechanisms of immune escape mediated by the PD-1 pathway. Leukemia 28:236–238CrossRefPubMed
96.
Zurück zum Zitat Holmström MO, Riley CH, Skov V, Svane IM, Hasselbalch HC, Andersen MH (2018) Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response. Oncoimmunology 7:e1433521CrossRefPubMedPubMedCentral Holmström MO, Riley CH, Skov V, Svane IM, Hasselbalch HC, Andersen MH (2018) Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response. Oncoimmunology 7:e1433521CrossRefPubMedPubMedCentral
97.
98.
Zurück zum Zitat Larsen SK, Munir S, Woetmann A, Frøsig TM, Odum N, Svane IM, Becker JC, Andersen MH (2013) Functional characterization of Foxp3-specific spontaneous immune responses. Leukemia 27:2332–2340CrossRefPubMed Larsen SK, Munir S, Woetmann A, Frøsig TM, Odum N, Svane IM, Becker JC, Andersen MH (2013) Functional characterization of Foxp3-specific spontaneous immune responses. Leukemia 27:2332–2340CrossRefPubMed
99.
Zurück zum Zitat Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989–999CrossRefPubMed Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989–999CrossRefPubMed
100.
Zurück zum Zitat Marty C, Lacout C, Droin N, Le Couédic J-P, Ribrag V et al (2013) A role for reactive oxygen species in JAK2V617F myeloproliferative neoplasm progression. Leukemia 27:2187–2195CrossRefPubMed Marty C, Lacout C, Droin N, Le Couédic J-P, Ribrag V et al (2013) A role for reactive oxygen species in JAK2V617F myeloproliferative neoplasm progression. Leukemia 27:2187–2195CrossRefPubMed
101.
Zurück zum Zitat Zhang X, Lv Z, Yu H, Zhu J (2017) The clinicopathological and prognostic role of thrombocytosis in patients with cancer: a meta-analysis. Oncol Lett 13:5002–5008CrossRefPubMedPubMedCentral Zhang X, Lv Z, Yu H, Zhu J (2017) The clinicopathological and prognostic role of thrombocytosis in patients with cancer: a meta-analysis. Oncol Lett 13:5002–5008CrossRefPubMedPubMedCentral
102.
Zurück zum Zitat Hasselbalch HC (2014) The platelet-cancer loop in myeloproliferative cancer. Is thrombocythemia an enhancer of cancer invasiveness and metastasis in essential thrombocythemia, polycythemia vera and myelofibrosis? Leuk Res 38:1230–1236CrossRefPubMed Hasselbalch HC (2014) The platelet-cancer loop in myeloproliferative cancer. Is thrombocythemia an enhancer of cancer invasiveness and metastasis in essential thrombocythemia, polycythemia vera and myelofibrosis? Leuk Res 38:1230–1236CrossRefPubMed
103.
Zurück zum Zitat Frederiksen H, Farkas DK, Christiansen CF, Larsen TS, Hasselbalch HC, Stentoft J, Sørensen HT (2015) Survival of patients with chronic myeloproliferative neoplasms and new primary cancers: a population-based cohort study. Lancet Haematol 2:e289–e296CrossRefPubMed Frederiksen H, Farkas DK, Christiansen CF, Larsen TS, Hasselbalch HC, Stentoft J, Sørensen HT (2015) Survival of patients with chronic myeloproliferative neoplasms and new primary cancers: a population-based cohort study. Lancet Haematol 2:e289–e296CrossRefPubMed
104.
Zurück zum Zitat Frederiksen H, Farkas DK, Christiansen CF, Hasselbalch HC, Sørensen HT, Sorensen HT (2011) Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study. Blood 118:6515–6520CrossRefPubMed Frederiksen H, Farkas DK, Christiansen CF, Hasselbalch HC, Sørensen HT, Sorensen HT (2011) Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study. Blood 118:6515–6520CrossRefPubMed
105.
Zurück zum Zitat Rachidi S, Metelli A, Riesenberg B, Wu BX, Nelson MH, Wallace C, Paulos CM, Rubinstein MP, Garrett-Mayer E, Hennig M, Bearden DW, Yang Y, Liu B, Li Z (2017) Platelets subvert T cell immunity against cancer via GARP-TGFβ axis. Sci Immunol 2:eaai7911CrossRefPubMedPubMedCentral Rachidi S, Metelli A, Riesenberg B, Wu BX, Nelson MH, Wallace C, Paulos CM, Rubinstein MP, Garrett-Mayer E, Hennig M, Bearden DW, Yang Y, Liu B, Li Z (2017) Platelets subvert T cell immunity against cancer via GARP-TGFβ axis. Sci Immunol 2:eaai7911CrossRefPubMedPubMedCentral
106.
Zurück zum Zitat Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72CrossRefPubMed Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72CrossRefPubMed
107.
Zurück zum Zitat Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Métivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefPubMed Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Métivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefPubMed
108.
Zurück zum Zitat Chen X, Fosco D, Kline DE, Kline J (2017) Calreticulin promotes immunity and type I interferon-dependent survival in mice with acute myeloid leukemia. Oncoimmunology. 6:e1278332CrossRefPubMedPubMedCentral Chen X, Fosco D, Kline DE, Kline J (2017) Calreticulin promotes immunity and type I interferon-dependent survival in mice with acute myeloid leukemia. Oncoimmunology. 6:e1278332CrossRefPubMedPubMedCentral
109.
Zurück zum Zitat Fucikova J, Truxova I, Hensler M, Becht E, Kasikova L, Moserova I, Vosahlikova S, Klouckova J, Church SE, Cremer I, Kepp O, Kroemer G, Galluzzi L, Salek C, Spisek R (2016) Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients. Blood 128:3113–3124PubMedPubMedCentral Fucikova J, Truxova I, Hensler M, Becht E, Kasikova L, Moserova I, Vosahlikova S, Klouckova J, Church SE, Cremer I, Kepp O, Kroemer G, Galluzzi L, Salek C, Spisek R (2016) Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients. Blood 128:3113–3124PubMedPubMedCentral
Metadaten
Titel
Cancer immune therapy for myeloid malignancies: present and future
verfasst von
Morten Orebo Holmström
Hans Carl Hasselbalch
Publikationsdatum
09.07.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 1/2019
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-018-0693-x

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