CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells

Journal of Clinical Investigation

Volumn 116, Issue 7, 2006, Pages 1935-1945

  Quezada, Sergio A ^a   Peggs, Karl S ^a   Curran, Michael A ^a   Allison, James P ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; TRANSCRIPTION FACTOR FOXP3; TUMOR VACCINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL INFILTRATION; CELL PROLIFERATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG MECHANISM; EFFECTOR CELL; FLOW CYTOMETRY; IMMUNOTHERAPY; IN VIVO STUDY; LYMPH NODE; LYMPHOCYTE PROLIFERATION; MELANOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TUMOR GROWTH; TUMOR IMMUNITY; TUMOR REJECTION;

ANIMALS; ANTIGENS, CD; ANTIGENS, CD4; ANTIGENS, CD8; ANTIGENS, DIFFERENTIATION; CANCER VACCINES; CELL LINE, TUMOR; CELL PROLIFERATION; FORKHEAD TRANSCRIPTION FACTORS; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; IMMUNOTHERAPY; LYMPH NODES; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

EID: 33745851479     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI27745     Document Type: Article

References (44)

1. Greenwald, R.J., Freeman, G.J., and Sharpe, A.H. 2005. The B7 family revisited. Annu. Rev. Immunol. 23:515-548.
2. Krummel, M.F., and Allison, J.P. 1996. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J. Exp. Med. 183:2533-2540.
3. Brunner, M.C., et al. 1999. CTLA-4-mediated inhibition of early events of T cell proliferation. J. Immunol. 162:5813-5820.
4. Greenwald, R.J., Boussiotis, V.A., Lorsbach, R.B., Abbas, A.K., and Sharpe, A.H. 2001. CTLA-4 regulates induction of anergy in vivo. Immunity. 14:145-155.
5. Egen, J.G., and Allison, J.P. 2002. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity. 16:23-35.
6. Egen, J.G., Kuhns, M.S., and Allison, J.P. 2002. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat. Immunol. 3:611-618.
7. Leach, D.R., Krummel, M.F., and Allison, J.P. 1996. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 271:1734-1736.
8. Kwon, E.D., et al. 1997. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl. Acad. Sci. U. S. A. 94:8099-8103.
9. Yang, Y.F., et al. 1997. Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages. Cancer Res. 57:4036-4041.
10. Shrikant, P., Khoruts, A., and Mescher, M.F. 1999. CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity. 11:483-493.
11. Sotomayor, E.M., Borrello, I., Tubb, E., Allison, J.P., and Levitsky, H.I. 1999. In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance. Proc. Natl. Acad. Sci. U. S. A. 96:11476-11481.
12. Van Elsas, A., Hurwitz, A.A., and Allison, J.P. 1999. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 190:355-366.
13. Hurwitz, A.A., Yu, T.F., Leach, D.R., and Allison, J.P. 1998. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc. Natl. Acad. Sci. U. S. A. 95:10067-10071.
14. Van Elsas, A., et al. 2001. Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: comparison of prophylaxis and therapy. J. Exp. Med. 194:481-489.
15. Dranoff, G., et al. 1993. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc. Natl. Acad. Sci. U. S. A. 90:3539-3543.
16. Huang, A.Y., et al. 1994. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science. 264:961-965.
17. Hodi, F.S., et al. 2003. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc. Natl. Acad. Sci. U. S. A. 100:4712-4717.
18. Ribas, A., et al. 2004. Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy. J. Immunother. 27:354-367.
19. Phan, G.Q., et al. 2003. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. U. S. A. 100:8372-8377.
20. Korman, A., Yellin, M., and Keler, T. 2005. Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies. Curr. Opin. Investig. Drugs. 6:582-591.
21. Peggs, K.S., Quezada, S.A., Korman, A.J., and Allison, J.P. 2006. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr. Opin. Immunol. 8:206-213.
22. 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.
23. Sakaguchi, S. 2005. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6:345-352.
24. Graca, L., Cobbold, S.P., and Waldmann, H. 2002. Identification of regulatory T cells in tolerated allografts. J. Exp. Med. 195:1641-1646.
25. Lee, I., et al. 2005. Recruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor. J. Exp. Med. 201:1037-1044.
26. 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.
27. Ko, K., et al. 2005. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J. Exp. Med. 202:885-891.
28. Viguier, M., et al. 2004. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J. Immunol. 173:1444-1453.
29. Sutmuller, R.P., et al. 2001. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J. Exp. Med. 194:823-832.
30. Read, S., Malmstrom, V., and Powrie, F. 2000. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J. Exp. Med. 192:295-302.
31. 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.
32. Kataoka, H., et al. 2005. CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4. Int. Immunol. 17:421-427.
33. Tang, Q., et al. 2004. Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function. Eur. J. Immunol. 34:2996-3005.
34. Maker, A.V., Attia, P., and Rosenberg, S.A. 2005. Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade. J. Immunol. 175:7746-7754.
35. Thornton, A.M., Piccirillo, C.A., and Shevach, E.M. 2004. Activation requirements for the induction of CD4+CD25+ T cell suppressor function. Eur. J. Immunol. 34:366-376.
36. Keler, T., et al. 2003. Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J. Immunol. 171:6251-6259.
37. Attia, P., et al. 2005. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J. Clin. Oncol. 23:6043-6053.
38. Ghiringhelli, F., et al. 2005. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J. Exp. Med. 202:919-929.
39. Dittmer, U., et al. 2004. Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection. Immunity. 20:293-303.
40. Piccirillo, C.A., and Shevach, E.M. 2001. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J. Immunol. 167:1137-1140.
41. Chen, M.L., et al. 2005. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc. Natl. Acad. Sci. U. S. A. 102:419-424.
42. Yu, P., et al. 2005. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J. Exp. Med. 201:779-791.
43. Chambers, C.A., Kuhns, M.S., and Allison, J.P. 1999. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4(+) T cell responses. Proc. Natl. Acad. Sci. U. S. A. 96:8603-8608.
44. Kowalczyk, D.W., et al. 2001. A method that allows easy characterization of tumor-infiltrating lymphocytes. J. Immunol. Methods. 253:163-175.