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Erschienen in: Breast Cancer Research 1/2005

01.02.2006 | Commentary

Dendritic cell defects in patients with cancer: mechanisms and significance

verfasst von: Corrine Lenahan, David Avigan

Erschienen in: Breast Cancer Research | Ausgabe 1/2005

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Abstract

Dendritic cells (DCs) are a complex network of antigen-presenting cells that have an essential role in the modulation of primary immunity. There has been increasing evidence that DCs isolated from patients with malignancy demonstrate functional deficiencies that inhibit the capacity to mount an effective anti-tumor response. In this issue of Breast Cancer Research, Pinzon-Charry and colleagues investigate one of the possible mechanisms by which tumors induce DC dysfunction to evade host immune surveillance. They demonstrate that DCs isolated from the circulation of patients with early-stage breast cancer exhibit increased rates of spontaneous apoptosis. In vitro studies suggest that a soluble factor secreted by breast cancer cells is responsible for this phenomenon. In contrast, ex vivo conditioning of DCs with CD-40 ligand and IL-12 was protective against tumor-induced apoptosis.
Literatur
1.
Zurück zum Zitat Avigan D: Dendritic cells: development, function and potential use for cancer immunotherapy. Blood Rev. 1999, 13: 51-64. 10.1016/S0268-960X(99)90023-1.CrossRefPubMed Avigan D: Dendritic cells: development, function and potential use for cancer immunotherapy. Blood Rev. 1999, 13: 51-64. 10.1016/S0268-960X(99)90023-1.CrossRefPubMed
2.
Zurück zum Zitat Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature. 1998, 392: 245-252. 10.1038/32588.CrossRefPubMed Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature. 1998, 392: 245-252. 10.1038/32588.CrossRefPubMed
3.
Zurück zum Zitat Knutson KL, Schiffman K, Cheever MA, Disis ML: Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide results in short-lived peptide-specific immunity. Clin Cancer Res. 2002, 8: 1014-1018.PubMed Knutson KL, Schiffman K, Cheever MA, Disis ML: Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide results in short-lived peptide-specific immunity. Clin Cancer Res. 2002, 8: 1014-1018.PubMed
4.
Zurück zum Zitat Boczkowski D, Nair SK, Snyder D, Gilboa E: Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med. 1996, 184: 465-472. 10.1084/jem.184.2.465.CrossRefPubMed Boczkowski D, Nair SK, Snyder D, Gilboa E: Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med. 1996, 184: 465-472. 10.1084/jem.184.2.465.CrossRefPubMed
5.
Zurück zum Zitat Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R: Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 1996, 2: 52-58. 10.1038/nm0196-52.CrossRefPubMed Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R: Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 1996, 2: 52-58. 10.1038/nm0196-52.CrossRefPubMed
6.
Zurück zum Zitat Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, et al: Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor-derived dendritic cell vaccine. Cancer Res. 2001, 61: 6451-6458.PubMed Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, et al: Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor-derived dendritic cell vaccine. Cancer Res. 2001, 61: 6451-6458.PubMed
7.
Zurück zum Zitat Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D: Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998, 4: 328-332. 10.1038/nm0398-328.CrossRefPubMed Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D: Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998, 4: 328-332. 10.1038/nm0398-328.CrossRefPubMed
8.
Zurück zum Zitat Brown RD, Pope B, Murray A, Esdale W, Sze DM, Gibson J, Ho PJ, Hart D, Joshua D: Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood. 2001, 98: 2992-2998. 10.1182/blood.V98.10.2992.CrossRefPubMed Brown RD, Pope B, Murray A, Esdale W, Sze DM, Gibson J, Ho PJ, Hart D, Joshua D: Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood. 2001, 98: 2992-2998. 10.1182/blood.V98.10.2992.CrossRefPubMed
9.
Zurück zum Zitat Gabrilovich DI, Ciernik IF, Carbone D: Dendritic cells in antitumor immune responses. I. Defective antigen presentation in tumor-bearing hosts. Cell Immunol. 1996, 170: 101-110. 10.1006/cimm.1996.0139.CrossRefPubMed Gabrilovich DI, Ciernik IF, Carbone D: Dendritic cells in antitumor immune responses. I. Defective antigen presentation in tumor-bearing hosts. Cell Immunol. 1996, 170: 101-110. 10.1006/cimm.1996.0139.CrossRefPubMed
10.
Zurück zum Zitat Hoffman TK, Muller-Berghaus J, Ferris RJ, Johnson JT, Storkus WJ, Whiteside TL: Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clin Cancer Res. 2002, 8: 1787-1793. Hoffman TK, Muller-Berghaus J, Ferris RJ, Johnson JT, Storkus WJ, Whiteside TL: Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clin Cancer Res. 2002, 8: 1787-1793.
11.
Zurück zum Zitat Troy AJ, Summers KL, Davidson PJ, Atkinson CH, Hart DN: Minimal recruitment and activation of dendritic cells withing renal cell carcinoma. Clin Cancer Res. 1998, 4: 585-593.PubMed Troy AJ, Summers KL, Davidson PJ, Atkinson CH, Hart DN: Minimal recruitment and activation of dendritic cells withing renal cell carcinoma. Clin Cancer Res. 1998, 4: 585-593.PubMed
12.
Zurück zum Zitat Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML: Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer. 2003, 89: 1463-1472. 10.1038/sj.bjc.6601243.CrossRefPubMed Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML: Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer. 2003, 89: 1463-1472. 10.1038/sj.bjc.6601243.CrossRefPubMed
13.
Zurück zum Zitat Troy A, Davidson P, Atkinson C, Hart D: Phenotypic characteristics of dendritic cell infiltrate in prostate cancer. J Urol. 1998, 160: 214-219. 10.1097/00005392-199807000-00087.CrossRefPubMed Troy A, Davidson P, Atkinson C, Hart D: Phenotypic characteristics of dendritic cell infiltrate in prostate cancer. J Urol. 1998, 160: 214-219. 10.1097/00005392-199807000-00087.CrossRefPubMed
14.
Zurück zum Zitat Chaux P, Favre N, Martin M, Martin F: Tumor-infiltrating dendritic cells are defective in their antigen presenting function and inducible B7 expression in rats. Int J Cancer. 1997, 72: 619-624. 10.1002/(SICI)1097-0215(19970807)72:4<619::AID-IJC12>3.0.CO;2-6.CrossRefPubMed Chaux P, Favre N, Martin M, Martin F: Tumor-infiltrating dendritic cells are defective in their antigen presenting function and inducible B7 expression in rats. Int J Cancer. 1997, 72: 619-624. 10.1002/(SICI)1097-0215(19970807)72:4<619::AID-IJC12>3.0.CO;2-6.CrossRefPubMed
15.
Zurück zum Zitat Pinzon-Charry A, Maxwell T, McGuckin MA, Schmidt C, Furnival C, Lopez JA: Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. Breast Cancer Res. 2006, 8: R5-10.1186/bcr1361.CrossRefPubMed Pinzon-Charry A, Maxwell T, McGuckin MA, Schmidt C, Furnival C, Lopez JA: Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. Breast Cancer Res. 2006, 8: R5-10.1186/bcr1361.CrossRefPubMed
16.
Zurück zum Zitat Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 1996, 2: 1096-1103. 10.1038/nm1096-1096.CrossRefPubMed Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 1996, 2: 1096-1103. 10.1038/nm1096-1096.CrossRefPubMed
17.
Zurück zum Zitat Steinbrink K, Graulich E, Kubsch S, Knop J, Enk A: CD4+ and CD8+ anergic T cells induced by interleukin-10-treated human dendritic cells display antigen specific suppressor activity. Blood. 2002, 99: 2468-2476. 10.1182/blood.V99.7.2468.CrossRefPubMed Steinbrink K, Graulich E, Kubsch S, Knop J, Enk A: CD4+ and CD8+ anergic T cells induced by interleukin-10-treated human dendritic cells display antigen specific suppressor activity. Blood. 2002, 99: 2468-2476. 10.1182/blood.V99.7.2468.CrossRefPubMed
18.
Zurück zum Zitat Portielje JE, Gratama JW, van Ojik HH, Stoter G, Kruit WH: IL-12: a promising adjuvant for cancer vaccination. Cancer Immunol Immunother. 2003, 53: 133-144. Portielje JE, Gratama JW, van Ojik HH, Stoter G, Kruit WH: IL-12: a promising adjuvant for cancer vaccination. Cancer Immunol Immunother. 2003, 53: 133-144.
19.
Zurück zum Zitat Pirtskhalaishvili G, Shurin GV, Eshe C, Cai Q, Salup RR, Bykovskaia SN, Lotze MT, Shurin MR: Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins. Br J Cancer. 2000, 83: 506-513. 10.1054/bjoc.2000.1289.CrossRefPubMedPubMedCentral Pirtskhalaishvili G, Shurin GV, Eshe C, Cai Q, Salup RR, Bykovskaia SN, Lotze MT, Shurin MR: Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins. Br J Cancer. 2000, 83: 506-513. 10.1054/bjoc.2000.1289.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Kikuchi T, Akasaki Y, Abe T, Fukuda T, Saotome H, Ryan JL, Kufe DW, Ohno T: Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant interleukin 12. J Immunother. 2004, 27: 452-459. 10.1097/00002371-200411000-00005.CrossRefPubMed Kikuchi T, Akasaki Y, Abe T, Fukuda T, Saotome H, Ryan JL, Kufe DW, Ohno T: Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant interleukin 12. J Immunother. 2004, 27: 452-459. 10.1097/00002371-200411000-00005.CrossRefPubMed
Metadaten
Titel
Dendritic cell defects in patients with cancer: mechanisms and significance
verfasst von
Corrine Lenahan
David Avigan
Publikationsdatum
01.02.2006
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 1/2005
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1375

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