Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma

Journal of Immunology

Volumn 191, Issue 4, 2013, Pages 2009-2017

  Ganesan, Anusha Preethi ^a,b   Johansson, Magnus ^a   Ruffell, Brian ^a   Beltran, Adam ^a,c   Lau, Jonathan ^a   Jablons, David M ^a   Coussens, Lisa M ^a,c,d  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BASILIXIMAB; CARBOPLATIN; CD4 ANTIGEN; CD45 ANTIGEN; CD8 ANTIGEN; GAMMA INTERFERON; GRANZYME A; GRANZYME B; OKT 8; PERFORIN; TRANSCRIPTION FACTOR FOXP3;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN ANTIBODY COMPLEX; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOTOXIC T LYMPHOCYTE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOCOMPETENT CELL; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; LYMPHOCYTE SUBPOPULATION; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T CELL DEPLETION; TRANSGENIC MOUSE; TUMOR ASSOCIATED LEUKOCYTE;

ADENOCARCINOMA; ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS, ALKYLATING; CARBOPLATIN; CARCINOMA, NON-SMALL-CELL LUNG; CD4-POSITIVE T-LYMPHOCYTES; CISPLATIN; CYTOTOXICITY, IMMUNOLOGIC; HUMANS; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; LUNG NEOPLASMS; LYMPHOCYTE COUNT; LYMPHOCYTE DEPLETION; LYMPHOCYTES, TUMOR-INFILTRATING; LYMPHOPENIA; MICE; MICE, MUTANT STRAINS; MICE, TRANSGENIC; RANDOM ALLOCATION; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, CYTOTOXIC; T-LYMPHOCYTES, REGULATORY; TUMOR ESCAPE; TUMOR MICROENVIRONMENT;

EID: 84881458660     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1301317     Document Type: Article

References (59)

1. Jemal, A., F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman. 2011. Global cancer statistics. CA Cancer J. Clin. 61: 69-90.
2. Fridman, W. H., F. Pagès, C. Sautès-Fridman, and J. Galon. 2012. The immune contexture in human tumours: impact on clinical outcome. Nat. Rev. Cancer 12: 298-306.
3. Johnson, S. K., K. M. Kerr, A. D. Chapman, M. M. Kennedy, G. King, J. S. Cockburn, and R. R. Jeffrey. 2000. Immune cell infiltrates and prognosis in primary carcinoma of the lung. Lung Cancer 27: 27-35.
4. Donnem, T., K. Al-Shibli, S. Andersen, S. Al-Saad, L. T. Busund, and R. M. Bremnes. 2010. Combination of low vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 expression and high lymphocyte infiltration is a strong and independent favorable prognostic factor in patients with nonsmall cell lung cancer. Cancer 116: 4318-4325.
5. Al-Shibli, K. I., T. Donnem, S. Al-Saad, M. Persson, R. M. Bremnes, and L. T. Busund. 2008. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin. Cancer Res. 14: 5220-5227.
6. Welsh, T. J., R. H. Green, D. Richardson, D. A. Waller, K. J. O'Byrne, and P. Bradding. 2005. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J. Clin. Oncol. 23: 8959-8967.
7. Kawai, O., G. Ishii, K. Kubota, Y. Murata, Y. Naito, T. Mizuno, K. Aokage, N. Saijo, Y. Nishiwaki, A. Gemma, et al. 2008. Predominant infiltration of macrophages and CD8(+) T cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer 113: 1387-1395.
8. Curiel, T. J., G. Coukos, L. Zou, X. Alvarez, P. Cheng, P. Mottram, M. Evdemon-Hogan, J. R. Conejo-Garcia, L. Zhang, M. Burow, et al. 2004. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10: 942-949.
9. Bates, G. J., S. B. Fox, C. Han, R. D. Leek, J. F. Garcia, A. L. Harris, and A. H. Banham. 2006. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J. Clin. Oncol. 24: 5373-5380.
10. Shen, Z., S. Zhou, Y. Wang, R. L. Li, C. Zhong, C. Liang, and Y. Sun. 2010. Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer. J. Cancer Res. Clin. Oncol. 136: 1585-1595.
11. Zhou, J., T. Ding, W. Pan, L. Y. Zhu, L. Li, and L. Zheng. 2009. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int. J. Cancer 125: 1640-1648.
12. Ruffell, B., D. G. DeNardo, N. I. Affara, and L. M. Coussens. 2010. Lymphocytes in cancer development: polarization towards pro-tumor immunity. Cytokine Growth Factor Rev. 21: 3-10.
13. Zou, W. 2006. Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol. 6: 295-307.
14. Deeb, K. K., A. M. Michalowska, C. Y. Yoon, S. M. Krummey, M. J. Hoenerhoff, C. Kavanaugh, M. C. Li, F. J. Demayo, I. Linnoila, C. X. Deng, et al. 2007. Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis. Cancer Res. 67: 8065-8080.
15. Magdaleno, S. M., G. Wang, V. L. Mireles, M. K. Ray, M. J. Finegold, and F. J. DeMayo. 1997. Cyclin-dependent kinase inhibitor expression in pulmonary Clara cells transformed with SV40 large T antigen in transgenic mice. Cell Growth Differ. 8: 145-155.
16. de Visser, K. E., L. V. Korets, and L. M. Coussens. 2005. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7: 411-423.
17. Andreu, P., M. Johansson, N. I. Affara, F. Pucci, T. Tan, S. Junankar, L. Korets, J. Lam, D. Tawfik, D. G. DeNardo, et al. 2010. FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 17: 121-134.
18. Ruffell, B., A. Au, H. S. Rugo, L. J. Esserman, E. S. Hwang, and L. M. Coussens. 2012. Leukocyte composition of human breast cancer. Proc. Natl. Acad. Sci. USA 109: 2796-2801.
19. DeNardo, D. G., D. J. Brennan, E. Rexhepaj, B. Ruffell, S. L. Shiao, S. F. Madden, W. M. Gallagher, N. Wadhwani, S. D. Keil, S. A. Junaid, et al. 2011. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 1: 54-67.
20. Brunkow, M. E., E. W. Jeffery, K. A. Hjerrild, B. Paeper, L. B. Clark, S. A. Yasayko, J. E. Wilkinson, D. Galas, S. F. Ziegler, and F. Ramsdell. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27: 68-73.
21. Kim, J., K. Lahl, S. Hori, C. Loddenkemper, A. Chaudhry, P. deRoos, A. Rudensky, and T. Sparwasser. 2009. Cutting edge: depletion of Foxp3+ cells leads to induction of autoimmunity by specific ablation of regulatory T cells in genetically targeted mice. J. Immunol. 183: 7631-7634.
22. Munn, D. H., and A. L. Mellor. 2004. IDO and tolerance to tumors. Trends Mol. Med. 10: 15-18.
23. Mellor, A. L., and D. Munn. 2004. Policing pregnancy: Tregs help keep the peace. Trends Immunol. 25: 563-565.
24. Travis, M. A., B. Reizis, A. C. Melton, E. Masteller, Q. Tang, J. M. Proctor, Y. Wang, X. Bernstein, X. Huang, L. F. Reichardt, et al. 2007. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449: 361-365.
25. Coombes, J. L., K. R. Siddiqui, C. V. Arancibia-Cárcamo, J. Hall, C. M. Sun, Y. Belkaid, and F. Powrie. 2007. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 204: 1757-1764.
26. Quezada, S. A., K. S. Peggs, T. R. Simpson, Y. Shen, D. R. Littman, and J. P. Allison. 2008. Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. J. Exp. Med. 205: 2125-2138.
27. Pegram, M. D., and D. J. Slamon. 1999. Combination therapy with trastuzumab (Herceptin) and cisplatin for chemoresistant metastatic breast cancer: evidence for receptor-enhanced chemosensitivity. Semin. Oncol. 26(Suppl. 12): 89-95.
28. Rosell, R., G. Robinet, A. Szczesna, R. Ramlau, M. Constenla, B. C. Mennecier, W. Pfeifer, K. J. O'Byrne, T. Welte, R. Kolb, et al. 2008. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann. Oncol. 19: 362-369.
29. Koebel, C. M., W. Vermi, J. B. Swann, N. Zerafa, S. J. Rodig, L. J. Old, M. J. Smyth, and R. D. Schreiber. 2007. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450: 903-907.
30. Daniel, D., C. Chiu, E. Giraudo, M. Inoue, L. A. Mizzen, N. R. Chu, and D. Hanahan. 2005. CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer. Cancer Res. 65: 2018-2025.
31. Girardi, M., D. Oppenheim, E. J. Glusac, R. Filler, A. Balmain, R. E. Tigelaar, and A. C. Hayday. 2004. Characterizing the protective component of the alphabeta T cell response to transplantable squamous cell carcinoma. J. Invest. Dermatol. 122: 699-706.
32. Daniel, D., N. Meyer-Morse, E. K. Bergsland, K. Dehne, L. M. Coussens, and D. Hanahan. 2003. Immune enhancement of skin carcinogenesis by CD4+ T cells. J. Exp. Med. 197: 1017-1028.
33. Shah, S., A. A. Divekar, S. P. Hilchey, H. M. Cho, C. L. Newman, S. U. Shin, H. Nechustan, P. M. Challita-Eid, B. M. Segal, K. H. Yi, and J. D. Rosenblatt. 2005. Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. Int. J. Cancer 117: 574-586.
34. Barbera-Guillem, E., M. B. Nelson, B. Barr, J. K. Nyhus, K. F. May, Jr., L. Feng, and J. W. Sampsel. 2000. B lymphocyte pathology in human colorectal cancer: experimental and clinical therapeutic effects of partial B cell depletion. Cancer Immunol. Immunother. 48: 541-549.
35. Schultz, K. R., J. P. Klarnet, R. S. Gieni, K. T. HayGlass, and P. D. Greenberg. 1990. The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia. Science 249: 921-923.
36. DiLillo, D. J., K. Yanaba, and T. F. Tedder. 2010. B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice. J. Immunol. 184: 4006-4016.
37. Schneider, T., S. Kimpfler, A. Warth, P. A. Schnabel, H. Dienemann, D. Schadendorf, H. Hoffmann, and V. Umansky. 2011. Foxp3(+) regulatory T cells and natural killer cells distinctly infiltrate primary tumors and draining lymph nodes in pulmonary adenocarcinoma. J. Thorac. Oncol. 6: 432-438.
38. Dimitrakopoulos, F. I., H. Papadaki, A. G. Antonacopoulou, A. Kottorou, A. D. Gotsis, C. Scopa, H. P. Kalofonos, and A. Mouzaki. 2011. Association of FOXP3 expression with non-small cell lung cancer. Anticancer Res. 31: 1677-1683.
39. Sun, J. C., M. A. Williams, and M. J. Bevan. 2004. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nat. Immunol. 5: 927-933.
40. Shedlock, D. J., and H. Shen. 2003. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300: 337-339.
41. Onizuka, S., I. Tawara, J. Shimizu, S. Sakaguchi, T. Fujita, and E. Nakayama. 1999. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 59: 3128-3133.
42. Shimizu, J., S. Yamazaki, and S. Sakaguchi. 1999. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 163: 5211-5218.
43. Golgher, D., E. Jones, F. Powrie, T. Elliott, and A. Gallimore. 2002. Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur. J. Immunol. 32: 3267-3275.
44. Casares, N., L. Arribillaga, P. Sarobe, J. Dotor, A. Lopez-Diaz de Cerio, I. Melero, J. Prieto, F. Borrás-Cuesta, and J. J. Lasarte. 2003. CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFNgamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination. J. Immunol. 171: 5931-5939.
45. Jones, E., M. Dahm-Vicker, A. K. Simon, A. Green, F. Powrie, V. Cerundolo, and A. Gallimore. 2002. Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun. 2: 1.
46. Beyer, M., and J. L. Schultze. 2006. Regulatory T cells in cancer. Blood 108: 804-811.
47. Ghiringhelli, F., C. Ménard, M. Terme, C. Flament, J. Taieb, N. Chaput, P. E. Puig, S. Novault, B. Escudier, E. Vivier, et al. 2005. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factorbeta-dependent manner. J. Exp. Med. 202: 1075-1085.
48. Teng, M. W., J. B. Swann, B. von Scheidt, J. Sharkey, N. Zerafa, N. McLaughlin, T. Yamaguchi, S. Sakaguchi, P. K. Darcy, and M. J. Smyth. 2010. Multiple antitumor mechanisms downstream of prophylactic regulatory T-cell depletion. Cancer Res. 70: 2665-2674.
49. Tadokoro, C. E., G. Shakhar, S. Shen, Y. Ding, A. C. Lino, A. Maraver, J. J. Lafaille, and M. L. Dustin. 2006. Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J. Exp. Med. 203: 505-511.
50. Mahajan, D., Y. Wang, X. Qin, Y. Wang, G. Zheng, Y. M. Wang, S. I. Alexander, and D. C. Harris. 2006. CD4+CD25+ regulatory T cells protect against injury in an innate murine model of chronic kidney disease. J. Am. Soc. Nephrol. 17: 2731-2741.
51. Tiemessen, M. M., A. L. Jagger, H. G. Evans, M. J. van Herwijnen, S. John, and L. S. Taams. 2007. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc. Natl. Acad. Sci. USA 104: 19446-19451.
52. Zhen, Y., J. Zheng, and Y. Zhao. 2008. Regulatory CD4+CD25+ T cells and macrophages: communication between two regulators of effector T cells. Inflamm. Res. 57: 564-570.
53. Tawara, I., Y. Take, A. Uenaka, Y. Noguchi, and E. Nakayama. 2002. Sequential involvement of two distinct CD4+ regulatory T cells during the course of transplantable tumor growth and protection from 3-methylcholanthrene-induced tumorigenesis by CD25-depletion. Jpn. J. Cancer Res. 93: 911-916.
54. Yu, P., Y. Lee, W. Liu, T. Krausz, A. Chong, H. Schreiber, and Y. X. Fu. 2005. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J. Exp. Med. 201: 779-791.
55. Zitvogel, L., L. Apetoh, F. Ghiringhelli, and G. Kroemer. 2008. Immunological aspects of cancer chemotherapy. Nat. Rev. Immunol. 8: 59-73.
56. Anraku, M., T. Tagawa, L. Wu, Z. Yun, S. Keshavjee, L. Zhang, M. R. Johnston, and M. de Perrot. 2010. Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignant mesothelioma. J. Immunol. 185: 956-966.
57. Teng, M. W., S. F. Ngiow, B. von Scheidt, N. McLaughlin, T. Sparwasser, and M. J. Smyth. 2010. Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res. 70: 7800-7809.
58. Klages, K., C. T. Mayer, K. Lahl, C. Loddenkemper, M. W. Teng, S. F. Ngiow, M. J. Smyth, A. Hamann, J. Huehn, and T. Sparwasser. 2010. Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma. Cancer Res. 70: 7788-7799.
59. Malchow, S., D. S. Leventhal, S. Nishi, B. I. Fischer, L. Shen, G. P. Paner, A. S. Amit, C. Kang, J. E. Geddes, J. P. Allison, et al. 2013. Aire-dependent thymic development of tumor-associated regulatory T cells. Science 339: 1219-1224.