Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma

Journal of Clinical Investigation

Volumn 119, Issue 11, 2009, Pages 3311-3321

  Bonertz, Andreas ^a   Weitz, Jürgen ^b   Pietsch, Dong Ho Kim ^a   Rahbari, Nuh N ^b   Schlude, Christoph ^a   Ge, Yingzi ^a   Juenger, Simone ^a   Vlodavsky, Israel ^c   Khazaie, Khashayarsha ^d   Jaeger, Dirk ^a   Reissfelder, Christoph ^b   Antolovic, Dalibor ^b   Aigner, Maximilian ^b   Koch, Moritz ^b   Beckhove, Philipp ^a  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^d NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SYNTHETIC PEPTIDE; TUMOR ANTIGEN;

ADULT; AGED; ANTIGEN RECOGNITION; ANTIGEN SPECIFICITY; ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; COLORECTAL CARCINOMA; CONTROLLED STUDY; EFFECTOR CELL; HUMAN; HUMAN CELL; HUMAN TISSUE; LYMPHOCYTE FUNCTION; MAJOR CLINICAL STUDY; MEMORY T LYMPHOCYTE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE;

AMINO ACID SEQUENCE; ANTIGENS, NEOPLASM; COLORECTAL NEOPLASMS; HISTOCOMPATIBILITY TESTING; HUMANS; LYMPHOCYTE DEPLETION; MOLECULAR SEQUENCE DATA; PEPTIDES; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY;

EID: 70449360735     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI39608     Document Type: Article

References (59)

1. Dunn, G.P., et al. 2002. Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. 3:991-998.
2. Banchereau, J., and Palucka, A.K. 2005. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol. 5:296-306. (Pubitemid 40516155)
3. Tacken, P.J., et al. 2007. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat. Rev. Immunol. 7:790-802.
4. Melief, C.J., and van der Burg, S.H. 2008. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat. Rev. Cancer. 8:351-360.
5. Faure, F., et al. 2009. Long-lasting cross-presentation of tumor antigen in human DC. Eur. J. Immunol. 39:380-390.
6. Bennett, S.R., et al. 1998. B cells directly tolerize CD8(+) T cells. J. Exp. Med. 188:1977-1983.
7. Bijker, M.S., et al. 2008. Superior induction of antitumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation. Eur. J. Immunol. 38:1033-1042.
8. Speetjens, F.M., et al. 2009. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clin. Cancer Res. 15:1086-1095.
9. Sakaguchi, S. 2004. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22:531-562. (Pubitemid 38680433)
10. Fontenot, J.D., Gavin, M.A., and Rudensky, A.Y. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4:330-336.
11. Hori, S., Nomura, T., and Sakaguchi, S. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science. 299:1057-1061. (Pubitemid 36222930)
12. Curiel, T.J., et al. 2004. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10:942-949.
13. Nummer, D., et al. 2007. Role of tumor endothelium in CD4+ CD25+ regulatory T cell infiltration of human pancreatic carcinoma. J. Natl. Cancer Inst. 99:1188-1199. (Pubitemid 47233069)
14. Hiraoka, N., et al. 2006. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin. Cancer Res. 12:5423-5434. (Pubitemid 44497257)
15. Sato, E., et al. 2005. Intraepithelial CD8+ tumorinfiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc. Natl. Acad. Sci. U. S. A. 102:18538-18543. (Pubitemid 43011261)
16. Gao, Q., et al. 2007. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol. 25:2586-2593. (Pubitemid 47041232)
17. Kobayashi, N., et al. 2007. FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin. Cancer Res. 13:902-911. (Pubitemid 46340366)
18. Needham, D.J., Lee, J.X., and Beilharz, M.W. 2006. Intra-tumoural regulatory T cells: a potential new target in cancer immunotherapy. Biochem. Biophys. Res. Commun. 343:684-691.
19. Kim, J.M., Rasmussen, J.P., and Rudensky, A.Y. 2007. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8:191-197.
20. Sakaguchi, S., et al. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155:1151-1164.
21. Clarke, S.L., et al. 2006. CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer. PLoS ONE. 1:e129.
22. Samy, E.T., et al. 2005. Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node. J. Exp. Med. 202:771-781.
23. Tang, Q., et al. 2006. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat. Immunol. 7:83-92. (Pubitemid 41823872)
24. Tarbell, K.V., et al. 2004. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199:1467-1477.
25. Zou, W. 2006. Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol. 6:295-307.
26. Vence, L., et al. 2007. Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc. Natl. Acad. Sci. U. S. A. 104:20884-20889.
27. Wang, H.Y., et al. 2004. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity. 20:107-118.
28. Wang, H.Y., et al. 2005. Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. J. Immunol. 174:2661-2670.
29. Rammensee, H., et al. 1999. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 50:213-219. (Pubitemid 30099526)
30. McKenzie, E.A. 2007. Heparanase: a target for drug discovery in cancer and inflammation. Br. J. Pharmacol. 151:1-14. (Pubitemid 46675998)
31. Klein, L., Khazaie, K., and von Boehmer, H. 2003. In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc. Natl. Acad. Sci. U. S. A. 100:8886-8891. (Pubitemid 36899193)
32. Welters, M.J., et al. 2008. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin. Cancer Res. 14:178-187.
33. Baker, C., et al. 2008. Human CD8 responses to a complete epitope set from preproinsulin: implications for approaches to epitope discovery. J. Clin. Immunol. 28:350-360.
34. Toma, A., et al. 2005. Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients. Proc. Natl. Acad. Sci. U. S. A. 102:10581-10586. (Pubitemid 41061597)
35. Sgouroudis, E., and Piccirillo, C.A. 2009. Control of type 1 diabetes by CD4(+)Foxp3(+) regulatory T cells: lessons from mouse models and implications for human disease. Diabetes Metab. Res. Rev. 25:208-218.
36. Cao, X., et al. 2007. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 27:635-646. (Pubitemid 47628832)
37. Collison, L.W., et al. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 450:566-569.
38. Deaglio, S., et al. 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204:1257-1265. (Pubitemid 46919862)
39. Kobie, J.J., et al. 2006. T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5′-adenosine monophosphate to adenosine. J. Immunol. 177:6780-6786.
40. Li, M.O., Wan, Y.Y., and Flavell, R.A. 2007. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity. 26:579-591.
41. Rubtsov, Y.P., et al. 2008. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 28:546-558.
42. Takahashi, T., et al. 2000. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 192:303-310. (Pubitemid 30470313)
43. Feuerer, M., et al. 2001. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat. Med. 7:452-458. (Pubitemid 32298548)
44. Brossart, P., et al. 1999. Identification of HLA-A2- restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies. Blood. 93:4309-4317. (Pubitemid 29279274)
45. Novellino, L., Castelli, C., and Parmiani, G. 2005. A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol. Immunother. 54:187-207. (Pubitemid 40174238)
46. Nagorsen, D., et al. 2003. Differences in T-cell immunity toward tumor-associated antigens in colorectal cancer and breast cancer patients. Int. J. Cancer. 105:221-225. (Pubitemid 36505325)
47. Schirle, M., et al. 2000. Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach. Eur. J. Immunol. 30:2216-2225. (Pubitemid 30655761)
48. Ries, J., et al. 2005. Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy. Int. J. Oncol. 26:817-824.
49. Fisk, B., et al. 1995. Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J. Exp. Med. 181:2109-2117.
50. Sommerfeldt, N., et al. 2006. The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients. Cancer Res. 66:8258-8265. (Pubitemid 44299195)
51. Andersen, M.H., et al. 2001. Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients. Cancer Res. 61:5964-5968.
52. Vonderheide, R.H. 2002. Telomerase as a universal tumor-associated antigen for cancer immunotherapy. Oncogene. 21:674-679. (Pubitemid 34146270)
53. Shomura, H., et al. 2004. Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients. Br. J. Cancer. 90:1563-1571. (Pubitemid 38648239)
54. Antonacopoulou, A.G., et al. 2008. EGFR, HER-2 and COX-2 levels in colorectal cancer. Histopathology. 53:698-706. (Pubitemid 352768714)
55. + p53 peptide-specific T cells and regulatory T cells at tumor sites. Cancer Immunol. Immunother. 54:1072-1081.
56. Naomoto, Y., et al. 2005. The role of heparanase in gastrointestinal cancer. Oncol. Rep. 14:3-8.
57. Beckhove, P., et al. 2004. Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors. J. Clin. Invest. 114:67-76. (Pubitemid 39071645)
58. Barnea, E., et al. 2002. Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor-specific antigens. Eur. J. Immunol. 32:213-222. (Pubitemid 34092839)
59. Hausmann, S., et al. 1999. Peptide recognition by two HLA-A2/Tax11-19-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures. J. Immunol. 162:5389-5397. (Pubitemid 29307147)