nach oben

Erschienen in:

22.01.2019 | Original Article

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

verfasst von: Julia Schollbach, Stefan Kircher, Armin Wiegering, Florian Seyfried, Ingo Klein, Andreas Rosenwald, Christoph-Thomas Germer, Stefan Löb

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated along the tumour invasive front, in the tumour centre and within the neoplastic cells and expressed as total scores. Of the tumour specimens evaluable for immunohistochemistry, 100% showed CD8+ lymphocyte infiltration and 93.4% stained positive for IDO1. Total IDO1 score positively correlated with total CD8 score for all three subsites (p = 0.002, Kendall-tau-b 0.357). A high total CD8 score was positively correlated with lower ypUICC-stages (p = 0.047) and lower ypT-categories (p = 0.032). Total IDO1 expression showed a clear trend towards a lower risk of recurrence (p = 0.078). A high total IDO1 score was an independent prognostic marker for prolonged disease-free survival (HR 0.38, p = 0.046) and a high total CD8 score for favourable overall survival (HR 0.16, p = 0.029). Analysis of the local CD8 and IDO1 expression profile may be a helpful tool in predicting prognosis for patients with locally advanced rectal cancer following neoadjuvant chemoradiation.

Nur mit Berechtigung zugänglich

Siegel RL, Miller KD, Jemal A (2017) Cancer Statistics, 2017. CA Cancer J Clin 67(1):7–30. https://doi.org/10.3322/caac.21387 CrossRefPubMed

Torre LA, Siegel RL, Ward EM, Jemal A (2016) Global Cancer Incidence and Mortality Rates and Trends–An Update. Cancer Epidemiol Biomarkers Prev 25(1):16–27. https://doi.org/10.1158/1055-9965.EPI-15-0578 CrossRefPubMed

Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1(8496):1479–1482CrossRefPubMed

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study G (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740. https://doi.org/10.1056/NEJMoa040694 CrossRefPubMed

Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. Dutch Colorectal Cancer N Engl J Med 345(9):638–646. https://doi.org/10.1056/NEJMoa010580 CrossRefPubMed

Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rodel C (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30(16):1926–1933. https://doi.org/10.1200/JCO.2011.40.1836 CrossRefPubMed

van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ, Dutch Colorectal Cancer G (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12(6):575–582. https://doi.org/10.1016/S1470-2045(11)70097-3 CrossRefPubMed

Smith JJ, Garcia-Aguilar J (2015) Advances and challenges in treatment of locally advanced rectal cancer. J Clin Oncol 33(16):1797–1808. https://doi.org/10.1200/JCO.2014.60.1054 CrossRefPubMedPubMedCentral

Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474. https://doi.org/10.1245/s10434-010-0985-4 CrossRefPubMed

10.

Nagtegaal ID, Quirke P, Schmoll HJ (2011) Has the new TNM classification for colorectal cancer improved care? Nat Rev Clin Oncol 9(2):119–123. https://doi.org/10.1038/nrclinonc.2011.157 CrossRefPubMed

11.

Benson AB 3rd, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, Cooper HS, Engstrom PF, Enzinger PC, Fakih MG, Fuchs CS, Grem JL, Hunt S, Leong LA, Lin E, Martin MG, May KS, Mulcahy MF, Murphy K, Rohren E, Ryan DP, Saltz L, Sharma S, Shibata D, Skibber JM, Small W Jr, Sofocleous CT, Venook AP, Willett CG, Freedman-Cass DA, Gregory KM (2012) Rectal cancer. J Natl Compr Canc Netw 10(12):1528–1564CrossRefPubMed

12.

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964. https://doi.org/10.1126/science.1129139 CrossRefPubMed

13.

Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pages F, Galon J (2011) Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 29(6):610–618. https://doi.org/10.1200/JCO.2010.30.5425 CrossRefPubMed

14.

Galon J, Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, Zlobec I, Berger A, Bifulco C, Botti G, Tatangelo F, Britten CM, Kreiter S, Chouchane L, Delrio P, Arndt H, Asslaber M, Maio M, Masucci GV, Mihm M, Vidal-Vanaclocha F, Allison JP, Gnjatic S, Hakansson L, Huber C, Singh-Jasuja H, Ottensmeier C, Zwierzina H, Laghi L, Grizzi F, Ohashi PS, Shaw PA, Clarke BA, Wouters BG, Kawakami Y, Hazama S, Okuno K, Wang E, O’Donnell-Tormey J, Lagorce C, Pawelec G, Nishimura MI, Hawkins R, Lapointe R, Lundqvist A, Khleif SN, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Palmqvist R, Nagtegaal ID, Wang Y, D’Arrigo C, Kopetz S, Sinicrope FA, Trinchieri G, Gajewski TF, Ascierto PA, Fox BA (2012) Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 10:205. https://doi.org/10.1186/1479-5876-10-205 CrossRefPubMedPubMedCentral

15.

Pages F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, Lugli A, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Borger E, Hartmann A, Geppert C, Kolwelter J, Merkel S, Grutzmann R, Van den Eynde M, Jouret-Mourin A, Kartheuser A, Leonard D, Remue C, Wang JY, Bavi P, Roehrl MHA, Ohashi PS, Nguyen LT, Han S, MacGregor HL, Hafezi-Bakhtiari S, Wouters BG, Masucci GV, Andersson EK, Zavadova E, Vocka M, Spacek J, Petruzelka L, Konopasek B, Dundr P, Skalova H, Nemejcova K, Botti G, Tatangelo F, Delrio P, Ciliberto G, Maio M, Laghi L, Grizzi F, Fredriksen T, Buttard B, Angelova M, Vasaturo A, Maby P, Church SE, Angell HK, Lafontaine L, Bruni D, El Sissy C, Haicheur N, Kirilovsky A, Berger A, Lagorce C, Meyers JP, Paustian C, Feng Z, Ballesteros-Merino C, Dijkstra J, van de Water C, van Lent-van Vliet S, Knijn N, Musina AM, Scripcariu DV, Popivanova B, Xu M, Fujita T, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Sargent DJ, Fox BA, Galon J (2018) International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 391(10135):2128–2139. https://doi.org/10.1016/S0140-6736(18)30789-X CrossRefPubMed

16.

Munn DH, Mellor AL (2013) Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 34(3):137–143. https://doi.org/10.1016/j.it.2012.10.001 CrossRefPubMed

17.

Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189(9):1363–1372CrossRefPubMedPubMedCentral

18.

Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL (2005) GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22(5):633–642. https://doi.org/10.1016/j.immuni.2005.03.013 CrossRefPubMed

19.

Metz R, Rust S, Duhadaway JB, Mautino MR, Munn DH, Vahanian NN, Link CJ, Prendergast GC (2012) IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: a novel IDO effector pathway targeted by D-1-methyl-tryptophan. Oncoimmunology 1(9):1460–1468. https://doi.org/10.4161/onci.21716 CrossRefPubMedPubMedCentral

20.

Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, Fioretti MC, Puccetti P (2002) T cell apoptosis by tryptophan catabolism. Cell Death Differ 9(10):1069–1077. https://doi.org/10.1038/sj.cdd.4401073 CrossRefPubMed

21.

Terness P, Bauer TM, Rose L, Dufter C, Watzlik A, Simon H, Opelz G (2002) Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 196(4):447–457CrossRefPubMedPubMedCentral

22.

Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, Orabona C, Bianchi R, Belladonna ML, Volpi C, Santamaria P, Fioretti MC, Puccetti P (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176(11):6752–6761CrossRefPubMed

23.

Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA (2010) An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 185(6):3190–3198. https://doi.org/10.4049/jimmunol.0903670 CrossRefPubMed

24.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013 CrossRefPubMed

25.

van Baren N, Van den Eynde BJ (2015) Tumoral immune resistance mediated by enzymes that degrade tryptophan. Cancer Immunol Res 3(9):978–985. https://doi.org/10.1158/2326-6066.CIR-15-0095 CrossRefPubMed

26.

Brandacher G, Perathoner A, Ladurner R, Schneeberger S, Obrist P, Winkler C, Werner ER, Werner-Felmayer G, Weiss HG, Gobel G, Margreiter R, Konigsrainer A, Fuchs D, Amberger A (2006) Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res 12(4):1144–1151. https://doi.org/10.1158/1078-0432.CCR-05-1966 CrossRefPubMed

27.

Ferdinande L, Decaestecker C, Verset L, Mathieu A, Moles Lopez X, Negulescu AM, Van Maerken T, Salmon I, Cuvelier CA, Demetter P (2012) Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer. Br J Cancer 106(1):141–147. https://doi.org/10.1038/bjc.2011.513 CrossRefPubMed

28.

Gao YF, Peng RQ, Li J, Ding Y, Zhang X, Wu XJ, Pan ZZ, Wan DS, Zeng YX, Zhang XS (2009) The paradoxical patterns of expression of indoleamine 2,3-dioxygenase in colon cancer. J Transl Med 7:71. https://doi.org/10.1186/1479-5876-7-71 CrossRefPubMedPubMedCentral

29.

Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R (2011) Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res 17(22):6985–6991. https://doi.org/10.1158/1078-0432.CCR-11-1331 CrossRefPubMed

30.

Schmiegel W, Buchberger B, Follmann M, Graeven U, Heinemann V, Langer T, Nothacker M, Porschen R, Rodel C, Rosch T, Schmitt W, Wesselmann S, Pox C (2017) S3-Leitlinie Kolorektales Karzinom. Z Gastroenterol 55(12):1344–1498. https://doi.org/10.1055/s-0043-121106 CrossRefPubMed

31.

Theate I, van Baren N, Pilotte L, Moulin P, Larrieu P, Renauld JC, Herve C, Gutierrez-Roelens I, Marbaix E, Sempoux C, Van den Eynde BJ (2015) Extensive profiling of the expression of the indoleamine 2,3-dioxygenase 1 protein in normal and tumoral human tissues. Cancer Immunol Res 3(2):161–172. https://doi.org/10.1158/2326-6066.CIR-14-0137 CrossRefPubMed

32.

Dahlin AM, Henriksson ML, Van Guelpen B, Stenling R, Oberg A, Rutegard J, Palmqvist R (2011) Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor. Mod Pathol 24(5):671–682. https://doi.org/10.1038/modpathol.2010.234 CrossRefPubMed

33.

Ling A, Edin S, Wikberg ML, Oberg A, Palmqvist R (2014) The intratumoural subsite and relation of CD8(+) and FOXP3(+) T lymphocytes in colorectal cancer provide important prognostic clues. Br J Cancer 110(10):2551–2559. https://doi.org/10.1038/bjc.2014.161 CrossRefPubMedPubMedCentral

34.

Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, Glickman JN, Ferrone CR, Mino-Kenudson M, Tanaka N, Dranoff G, Giovannucci EL, Fuchs CS (2009) Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res 15(20):6412–6420. https://doi.org/10.1158/1078-0432.CCR-09-1438 CrossRefPubMedPubMedCentral

35.

Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353(25):2654–2666. https://doi.org/10.1056/NEJMoa051424 CrossRefPubMed

36.

Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D’Arrigo C, Vidal-Vanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pages F (2014) Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 232(2):199–209. https://doi.org/10.1002/path.4287 CrossRefPubMed

37.

Galon J, Pages F, Marincola FM, Thurin M, Trinchieri G, Fox BA, Gajewski TF, Ascierto PA (2012) The immune score as a new possible approach for the classification of cancer. J Transl Med 10:1. https://doi.org/10.1186/1479-5876-10-1 CrossRefPubMedPubMedCentral

38.

Church SE, Galon J (2017) Regulation of CTL Infiltration Within the Tumor Microenvironment. Adv Exp Med Biol 1036:33–49. https://doi.org/10.1007/978-3-319-67577-0_3 CrossRefPubMed

39.

Lob S, Konigsrainer A, Schafer R, Rammensee HG, Opelz G, Terness P (2008) Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells. Blood 111(4):2152–2154. https://doi.org/10.1182/blood-2007-10-116111 CrossRefPubMed

40.

Lob S, Konigsrainer A, Zieker D, Brucher BL, Rammensee HG, Opelz G, Terness P (2009) IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother 58(1):153–157. https://doi.org/10.1007/s00262-008-0513-6 CrossRefPubMed

41.

Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8 + T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58(16):3491–3494PubMed

42.

Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T (2014) Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 14(2):135–146. https://doi.org/10.1038/nrc3670 CrossRefPubMed

43.

Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G (2015) Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell 28(6):690–714. https://doi.org/10.1016/j.ccell.2015.10.012 CrossRefPubMed

44.

Frey B, Ruckert M, Deloch L, Ruhle PF, Derer A, Fietkau R, Gaipl US (2017) Immunomodulation by ionizing radiation-impact for design of radio-immunotherapies and for treatment of inflammatory diseases. Immunol Rev 280(1):231–248. https://doi.org/10.1111/imr.12572 CrossRefPubMed

45.

Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281(5380):1191–1193CrossRefPubMed

46.

Ravishankar B, Liu H, Shinde R, Chandler P, Baban B, Tanaka M, Munn DH, Mellor AL, Karlsson MC, McGaha TL (2012) Tolerance to apoptotic cells is regulated by indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A 109(10):3909–3914. https://doi.org/10.1073/pnas.1117736109 CrossRefPubMedPubMedCentral

47.

Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9(10):1269–1274. https://doi.org/10.1038/nm934 CrossRefPubMed

48.

Baban B, Chandler P, McCool D, Marshall B, Munn DH, Mellor AL (2004) Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J Reprod Immunol 61(2):67–77. https://doi.org/10.1016/j.jri.2003.11.003 CrossRefPubMed

49.

de Faudeur G, de Trez C, Muraille E, Leo O (2008) Normal development and function of dendritic cells in mice lacking IDO-1 expression. Immunol Lett 118(1):21–29. https://doi.org/10.1016/j.imlet.2008.02.006 CrossRefPubMed

50.

Lob S, Konigsrainer A, Rammensee HG, Opelz G, Terness P (2009) Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer 9(6):445–452. https://doi.org/10.1038/nrc2639 CrossRefPubMed

51.

Monjazeb AM, Kent MS, Grossenbacher SK, Mall C, Zamora AE, Mirsoian A, Chen M, Kol A, Shiao SL, Reddy A, Perks JR, W TNC, Sparger EE, Canter RJ, Sckisel GD, Murphy WJ (2016) Blocking indolamine-2,3-dioxygenase rebound immune suppression boosts antitumor effects of radio-immunotherapy in murine models and spontaneous canine malignancies. Clin Cancer Res 22(17):4328–4340. https://doi.org/10.1158/1078-0432.CCR-15-3026 CrossRefPubMedPubMedCentral

52.

Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF (2013) Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 5(200):200ra116. https://doi.org/10.1126/scitranslmed.3006504 CrossRefPubMedPubMedCentral

53.

Gajewski TF, Louahed J, Brichard VG (2010) Gene signature in melanoma associated with clinical activity: a potential clue to unlock cancer immunotherapy. Cancer J 16(4):399–403. https://doi.org/10.1097/PPO.0b013e3181eacbd8 CrossRefPubMed

54.

Netter J, Douard R, Durdux C, Landi B, Berger A, Taieb J (2016) Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice. Clin Res Hepatol Gastroenterol 40(5):546–552. https://doi.org/10.1016/j.clinre.2016.03.004 CrossRefPubMed

55.

Sorensen RB, Berge-Hansen L, Junker N, Hansen CA, Hadrup SR, Schumacher TN, Svane IM, Becker JC, thor Straten P, Andersen MH (2009) The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. PLoS One 4(9):e6910. https://doi.org/10.1371/journal.pone.0006910 CrossRefPubMedPubMedCentral

56.

Sorensen RB, Hadrup SR, Svane IM, Hjortso MC, Thor Straten P, Andersen MH (2011) Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators. Blood 117(7):2200–2210. https://doi.org/10.1182/blood-2010-06-288498 CrossRefPubMedPubMedCentral

57.

Andersen MH, Svane IM (2015) Indoleamine 2,3-dioxygenase vaccination. Oncoimmunology 4(1):e983770. https://doi.org/10.4161/2162402X.2014.983770 CrossRefPubMedPubMedCentral

58.

Iversen TZ, Engell-Noerregaard L, Ellebaek E, Andersen R, Larsen SK, Bjoern J, Zeyher C, Gouttefangeas C, Thomsen BM, Holm B, Thor Straten P, Mellemgaard A, Andersen MH, Svane IM (2014) Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase. Clin Cancer Res 20(1):221–232. https://doi.org/10.1158/1078-0432.CCR-13-1560 CrossRefPubMed

59.

Vacchelli E, Aranda F, Eggermont A, Sautes-Fridman C, Tartour E, Kennedy EP, Platten M, Zitvogel L, Kroemer G, Galluzzi L (2014) Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology 3(10):e957994. https://doi.org/10.4161/21624011.2014.957994 CrossRefPubMedPubMedCentral

60.

Prendergast GC, Mondal A, Dey S, Laury-Kleintop LD, Muller AJ (2018) Inflammatory Reprogramming with IDO1 Inhibitors: Turning Immunologically Unresponsive ‘Cold’ Tumors ‘Hot’. Trends Cancer 4(1):38–58. https://doi.org/10.1016/j.trecan.2017.11.005 CrossRefPubMed

61.

Muller AJ, Manfredi MG, Zakharia Y, Prendergast GC (2018) Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and beyond. Semin Immunopathol. https://doi.org/10.1007/s00281-018-0702-0 CrossRefPubMed

62.

Companies Scaling Back IDO1 Inhibitor Trials (2018) Cancer Discov 8(7):OF5. https://doi.org/10.1158/2159-8290.CD-ND2018-007 CrossRef

Titel: Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?
verfasst von: Julia Schollbach
Stefan Kircher
Armin Wiegering
Florian Seyfried
Ingo Klein
Andreas Rosenwald
Christoph-Thomas Germer
Stefan Löb
Publikationsdatum: 22.01.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 4/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02306-y

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

Abstract

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2019

How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions

MDSCs in infectious diseases: regulation, roles, and readjustment

Mutations resulting in the formation of hyperactive complement convertases support cytocidal effect of anti-CD20 immunotherapeutics

Role of myeloid regulatory cells (MRCs) in maintaining tissue homeostasis and promoting tolerance in autoimmunity, inflammatory disease and transplantation

A potential role for peripheral natural killer cell activity induced by preoperative chemotherapy in breast cancer patients

The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie