Regulatory T cells in radiotherapeutic responses

Frontiers in Oncology

Volumn 2 AUG, Issue , 2012, Pages

  Schaue, Dörthe ^a   Xie, Michael W ^a   Ratikan, Josephine A ^a   McBride, William H ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Danger; radiation; Tregs

Indexed keywords

CELL ADHESION MOLECULE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 12; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MICRORNA; TOLL LIKE RECEPTOR;

ANGIOGENESIS; APOPTOSIS; CELL DIFFERENTIATION; CELL MATURATION; EPIGENETICS; HOMEOSTASIS; HUMAN; IMMUNE DEFICIENCY; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; NEOPLASM; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; TISSUE INJURY; TUMOR GROWTH; TUMOR VOLUME; WOUND HEALING;

EID: 84874727635     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2012.00090     Document Type: Review

References (147)

1. Ahn, G. O., Tseng, D., Liao, C. H., Dorie, M. J., Czechowicz, A., and Brown, J. M. (2010). Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc. Natl. Acad. Sci. U.S.A. 107, 8363-8368.
2. Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., Mignot, G., Maiuri, M. C., Ullrich, E., Saulnier, P., Yang, H., Amigorena, S., Ryffel, B., Barrat, F. J., Saftig, P., Levi, F., Lidereau, R., Nogues, C., Mira, J. P., Chompret, A., Joulin, V., Clavel-Chapelon, F., Bourhis, J., Andre, F., Delaloge, S., Tursz, T., Kroemer, G., and Zitvogel, L. (2007). Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13, 1050-1059.
3. Apostolou, I., and von Boehmer, H. (2004). In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 199, 1401-1408.
4. Awwad, M., and North, R. J. (1989). Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells. Cancer Res. 49, 1649-1654.
5. Banchereau, J., and Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature 392, 245-252.
6. Beal, A. M., Ramos-Hernandez, N., Riling, C. R., Nowelsky, E. A., and Oliver, P. M. (2012). TGF-beta induces the expression of the adaptor Ndfip1 to silence IL-4 production during iT(reg) cell differentiation. Nat. Immunol. 13, 77-85.
7. Belka, C., Ottinger, H., Kreuzfelder, E., Weinmann, M., Lindemann, M., Lepple-Wienhues, A., Budach, W., Grosse-Wilde, H., and Bamberg, M. (1999). Impact of localized radiotherapy on blood immune cells counts and function in humans. Radiother. Oncol. 50, 199-204.
8. Beutler, B. A. (2009). TLRs and innate immunity. Blood 113, 1399-1407.
9. Billiard, F., Buard, V., Benderitter, M., and Linard, C. (2011). Abdominal gamma-radiation induces an accumulation of function-impaired regulatory T cells in the small intestine. Int. J. Radiat. Oncol. Biol. Phys. 80, 869-876.
10. Bluestone, J. A., and Abbas, A. K. (2003). Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3, 253-257.
11. Bonavida, B., Hutchinson, I. V., and Thomas, A. (1979). Cyclophosphamide-sensitive and cyclophosphamide-resistant suppressor cells in the immune response to alloantigens. Transplant. Proc. 11, 874-877.
12. Burnette, B. C., Liang, H., Lee, Y., Chlewicki, L., Khodarev, N. N., Weichselbaum, R. R., Fu, Y. X., and Auh, S. L. (2011). The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res. 71, 2488-2496.
13. Byrne, W. L., Mills, K. H., Lederer, J. A., and O'Sullivan, G. C. (2011). Targeting regulatory T cells in cancer. Cancer Res. 71, 6915-6920.
14. Cao, M., Cabrera, R., Xu, Y., Liu, C., and Nelson, D. (2009). Gamma irradiation alters the phenotype and function of CD4+CD25+ regulatory T cells. Cell Biol. Int. 33, 565-571.
15. Chakraborty, M., Abrams, S. I., Camphausen, K., Liu, K., Scott, T., Coleman, C. N., and Hodge, J. W. (2003). Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J. Immunol. 170, 6338-6347.
16. Chakraborty, M., Abrams, S. I., Coleman, C. N., Camphausen, K., Schlom, J., and Hodge, J. W. (2004). External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res. 64, 4328-4337.
17. Chatila, T. A. (2009). Regulatory T cells: key players in tolerance and autoimmunity. Endocrinol. Metab. Clin. North Am. 38, 265-272, vii.
18. Chen, F. H., Chiang, C. S., Wang, C. C., Tsai, C. S., Jung, S. M., Lee, C. C., McBride, W. H., and Hong, J. H. (2009). Radiotherapy decreases vascular density and causes hypoxia with macrophage aggregation in TRAMP-C1 prostate tumors. Clin. Cancer Res. 15, 1721-1729.
19. Chen, M. L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H., and Khazaie, K. (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.
20. Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G., and Wahl, S. M. (2003). Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 198, 1875-1886.
21. Chiang, C. S., Fu, S. Y., Wang, S. C., Yu, C. F., Chen, F. H., Ling, C. M., and Hong, J. H. (2012). Irradiation promotes M2 macrophages toward hypoxia. Front. Oncol. 2:89. doi:10.3389/fonc.2012.00089
22. Conejo-Garcia, J. R., Benencia, F., Courreges, M. C., Kang, E., Mohamed-Hadley, A., Buckanovich, R. J., Holtz, D. O., Jenkins, A., Na, H., Zhang, L., Wagner, D. S., Katsaros, D., Caroll, R., and Coukos, G. (2004). Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat. Med. 10, 950-958.
23. Cronstein, B. N. (1994). Adenosine, an endogenous anti-inflammatory agent. J. Appl. Physiol. 76, 5-13.
24. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., Zhu, Y., Wei, S., Kryczek, I., Daniel, B., Gordon, A., Myers, L., Lackner, A., Disis, M. L., Knutson, K. L., Chen, L., and Zou, W. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942-949.
25. Curotto de Lafaille, M. A., and Lafaille, J. J. (2009). Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30, 626-635.
26. Curotto de Lafaille, M. A., Lino, A. C., Kutchukhidze, N., and Lafaille, J. J. (2004). CD25-T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J. Immunol. 173, 7259-7268.
27. Curotto de Lafaille, M. A., Muriglan, S., Sunshine, M. J., Lei, Y., Kutchukhidze, N., Furtado, G. C., Wensky, A. K., Olivares-Villagomez, D., and Lafaille, J. J. (2001). Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes. J. Exp. Med. 194, 1349-1359.
28. Curtin, J. F., Liu, N., Candolfi, M., Xiong, W., Assi, H., Yagiz, K., Edwards, M. R., Michelsen, K. S., Kroeger, K. M., Liu, C., Muhammad, A. K., Clark, M. C., Arditi, M., Comin-Anduix, B., Ribas, A., Lowenstein, P. R., and Castro, M. G. (2009). HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med. 6, e10. doi:10.1371/journal.pmed.1000010
29. Czerniecki, B. J., Cohen, P. A., Faries, M., Xu, S., Roros, J. G., and Bedrosian, I. (2001). Diverse functional activity of CD83+ monocyte-derived dendritic cells and the implications for cancer vaccines. Crit. Rev. Immunol. 21, 157-178.
30. Dang, E. V., Barbi, J., Yang, H. Y., Jinasena, D., Yu, H., Zheng, Y., Bordman, Z., Fu, J., Kim, Y., Yen, H. R., Luo, W., Zeller, K., Shimoda, L., Topalian, S. L., Semenza, G. L., Dang, C. V., Pardoll, D. M., and Pan, F. (2011). Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146, 772-784.
31. Dannull, J., Su, Z., Rizzieri, D., Yang, B. K., Coleman, D., Yancey, D., Zhang, A., Dahm, P., Chao, N., Gilboa, E., and Vieweg, J. (2005). Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 115, 3623-3633.
32. Deaglio, S., Dwyer, K. M., Gao, W., Friedman, D., Usheva, A., Erat, A., Chen, J. F., Enjyoji, K., Linden, J., Oukka, M., Kuchroo, V. K., Strom, T. B., and Robson, S. C. (2007). Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204, 1257-1265.
33. Debucquoy, A., Goethals, L., Geboes, K., Roels, S., McBride, W. H., and Haustermans, K. (2006). Molecular responses of rectal cancer to preoperative chemoradiation. Radiother. Oncol. 80, 172-177.
34. Debucquoy, A., Roels, S., Goethals, L., Libbrecht, L., Van Cutsem, E., Geboes, K., Penninckx, F., D'Hoore, A., McBride, W. H., and Haustermans, K. (2009). Double blind randomized phase II study with radiation+5-fluorouracil+/-celecoxib for resectable rectal cancer. Radiother. Oncol. 93, 273-278.
35. Deleeuw, R. J., Kost, S. E., Kakal, J. A., and Nelson, B. H. (2012). The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. Clin. Cancer Res. 18, 3022-3029.
36. Demaria, S., Kawashima, N., Yang, A. M., Devitt, M. L., Babb, J. S., Allison, J. P., and Formenti, S. C. (2005). Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin. Cancer Res. 11, 728-734.
37. Dewan, M. Z., Galloway, A. E., Kawashima, N., Dewyngaert, J. K., Babb, J. S., Formenti, S. C., and Demaria, S. (2009). Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin. Cancer Res. 15, 5379-5388.
38. Dewhirst, M. W., Oliver, R., Tso, C. Y., Gustafson, C., Secomb, T., and Gross, J. F. (1990). Heterogeneity in tumor microvascular response to radiation. Int. J. Radiat. Oncol. Biol. Phys. 18, 559-568.
39. Efimova, O., Szankasi, P., and Kelley, T. W. (2011). Ncf1 (p47phox) is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells. PLoS ONE 6, e16013. doi:10.1371/journal.pone.0016013
40. Facciabene, A., Peng, X., Hagemann, I. S., Balint, K., Barchetti, A., Wang, L. P., Gimotty, P. A., Gilks, C. B., Lal, P., Zhang, L., and Coukos, G. (2011). Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 475, 226-230.
41. Fernandez-Botran, R., Sanders, V. M., Mosmann, T. R., and Vitetta, E. S. (1988). Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J. Exp. Med. 168, 543-558.
42. Ferrara, T. A., Hodge, J. W., and Gulley, J. L. (2009). Combining radiation and immunotherapy for synergistic antitumor therapy. Curr. Opin. Mol. Ther. 11, 37-42.
43. Feuerer, M., Hill, J. A., Kretschmer, K., von Boehmer, H., Mathis, D., and Benoist, C. (2010). Genomic definition of multiple ex vivo regulatory T cell subphenotypes. Proc. Natl. Acad. Sci. U.S.A. 107, 5919-5924.
44. Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J., Schlawe, K., Chang, H. D., Bopp, T., Schmitt, E., Klein-Hessling, S., Serfling, E., Hamann, A., and Huehn, J. (2007). Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5, e38. doi:10.1371/journal.pbio.0050038
45. Fontenot, J. D., and Rudensky, A. Y. (2005). A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat. Immunol. 6, 331-337.
46. Formenti, S. C., and Demaria, S. (2009). Systemic effects of local radiotherapy. Lancet Oncol. 10, 718-726.
47. Gallucci, S., Lolkema, M., and Matzinger, P. (1999). Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5, 1249-1255.
48. 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, P. H., Trajanoski, Z., Fridman, W. H., and Pages, F. (2006). Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960-1964.
49. Gao, Y., Lin, F., Su, J., Gao, Z., Li, Y., Yang, J., Deng, Z., Liu, B., Tsun, A., and Li, B. (2012). Molecular mechanisms underlying the regulation and functional plasticity of FOXP3(+) regulatory T cells. Genes Immun. 13, 1-13.
50. Garcia-Barros, M., Paris, F., Cordon-Cardo, C., Lyden, D., Rafii, S., Haimovitz-Friedman, A., Fuks, Z., and Kolesnick, R. (2003). Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 300, 1155-1159.
51. Garnett, C. T., Palena, C., Chakraborty, M., Tsang, K. Y., Schlom, J., and Hodge, J. W. (2004). Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 64, 7985-7994.
52. Gershon, R. K., and Kondo, K. (1971). Infectious immunological tolerance. Immunology 21, 903-914.
53. Haribhai, D., Lin, W., Edwards, B., Ziegelbauer, J., Salzman, N. H., Carlson, M. R., Li, S. H., Simpson, P. M., Chatila, T. A., and Williams, C. B. (2009). A central role for induced regulatory T cells in tolerance induction in experimental colitis. J. Immunol. 182, 3461-3468.
54. Haribhai, D., Williams, J. B., Jia, S., Nickerson, D., Schmitt, E. G., Edwards, B., Ziegelbauer, J., Yassai, M., Li, S. H., Relland, L. M., Wise, P. M., Chen, A., Zheng, Y. Q., Simpson, P. M., Gorski, J., Salzman, N. H., Hessner, M. J., Chatila, T. A., and Williams, C. B. (2011). A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 35, 109-122.
55. Hellstrom, K. E., Hellstrom, I., Kant, J. A., and Tamerius, J. D. (1978). Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population. J. Exp. Med. 148, 799-804.
56. Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., Akerley, W., van den Eertwegh, A. J., Lutzky, J., Lorigan, P., Vaubel, J. M., Linette, G. P., Hogg, D., Ottensmeier, C. H., Lebbe, C., Peschel, C., Quirt, I., Clark, J. I., Wolchok, J. D., Weber, J. S., Tian, J., Yellin, M. J., Nichol, G. M., Hoos, A., and Urba, W. J. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711-723.
57. Hofer, M., Pospisil, M., Znojil, V., Vacek, A., Weiterova, L., Hola, J., and Vacha, J. (2002). Drugs elevating extracellular adenosine promote regeneration of haematopoietic progenitor cells in severely myelosuppressed mice: their comparison and joint effects with the granulocyte colony-stimulating factor. Eur. J. Haematol. 68, 4-11.
58. Hosek, B., Bohacek, J., Sikulova, J., Pospisil, M., and Vacek, A. (1992). Protection of early cellular damage in 1 Gy-irradiated mice by the elevation of extracellular adenosine. Radiat. Environ. Biophys. 31, 289-297.
59. Hou, B., Xu, Z. W., Yang, C. W., Gao, Y., Zhao, S. F., and Zhang, C. G. (2007). Protective effects of inosine on mice subjected to lethal total-body ionizing irradiation. J. Radiat. Res. 48, 57-62.
60. Housley, W. J., Adams, C. O., Nichols, F. C., Puddington, L., Lingenheld, E. G., Zhu, L., Rajan, T. V., and Clark, R. B. (2011). Natural but not inducible regulatory T cells require TNF-alpha signaling for in vivo function. J. Immunol. 186, 6779-6787.
61. Howie, S., and McBride, W. H. (1982). Tumor-specific T helper activity can be abrogated by two distinct suppressor cell mechanisms. Eur. J. Immunol. 12, 671-675.
62. Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., and Minato, N. (2002). Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. U.S.A. 99, 12293-12297.
63. Josefowicz, S. Z., Niec, R. E., Kim, H. Y., Treuting, P., Chinen, T., Zheng, Y., Umetsu, D. T., and Rudensky, A. Y. (2012). Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482, 395-399.
64. Kachikwu, E. L., Iwamoto, K. S., Liao, Y. P., Demarco, J. J., Agazaryan, N., Economou, J. S., McBride, W. H., and Schaue, D. (2011). Radiation enhances regulatory T Cell representation. Int. J. Radiat. Oncol. Biol. Phys. 81, 1128-1135.
65. Kandalaft, L. E., Motz, G. T., Busch, J., and Coukos, G. (2011). Angiogenesis and the tumor vasculature as antitumor immune modulators: the role of vascular endothelial growth factor and endothelin. Curr. Top. Microbiol. Immunol. 344, 129-148.
66. Kawai, T., and Akira, S. (2011). Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650.
67. Kioi, M., Vogel, H., Schultz, G., Hoffman, R. M., Harsh, G. R., and Brown, J. M. (2010). Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J. Clin. Invest. 120, 694-705.
68. Kusunoki, Y., Yamaoka, M., Kubo, Y., Hayashi, T., Kasagi, F., Douple, E. B., and Nakachi, K. (2010). T-cell immunosenescence and inflammatory response in atomic bomb survivors. Radiat. Res. 174, 870-876.
69. Ladoire, S., Martin, F., and Ghiringhelli, F. (2011). Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer. Cancer Immunol. Immunother. 60, 909-918.
70. Leach, D. R., Krummel, M. F., and Allison, J. P. (1996). Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734-1736.
71. Lee, Y., Auh, S. L., Wang, Y., Burnette, B., Meng, Y., Beckett, M., Sharma, R., Chin, R., Tu, T., Weichselbaum, R. R., and Fu, Y. X. (2009). Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114, 589-595.
72. Litjens, N. H., Boer, K., and Betjes, M. G. (2012). Identification of circulating human antigen-reactive CD4+FOXP3+ natural regulatory T cells. J. Immunol. 188, 1083-1090.
73. Liyanage, U. K., Moore, T. T., Joo, H. G., Tanaka, Y., Herrmann, V., Doherty, G., Drebin, J. A., Strasberg, S. M., Eberlein, T. J., Goedegebuure, P. S., and Linehan, D. C. (2002). Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol. 169, 2756-2761.
74. Lorimore, S. A., Coates, P. J., Scobie, G. E., Milne, G., and Wright, E. G. (2001). Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? Oncogene 20, 7085-7095.
75. Lotze, M. T., Zeh, H. J., Rubartelli, A., Sparvero, L. J., Amoscato, A. A., Washburn, N. R., Devera, M. E., Liang, X., Tor, M., and Billiar, T. (2007). The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol. Rev. 220, 60-81.
76. Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger, J. G., and Lord, E. M. (2005). Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J. Immunol. 174, 7516-7523.
77. Lugade, A. A., Sorensen, E. W., Gerber, S. A., Moran, J. P., Frelinger, J. G., and Lord, E. M. (2008). Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J. Immunol. 180, 3132-3139.
78. Mandapathil, M., Szczepanski, M. J., Szajnik, M., Ren, J., Lenzner, D. E., Jackson, E. K., Gorelik, E., Lang, S., Johnson, J. T., and Whiteside, T. L. (2009). Increased ectonucleotidase expression and activity in regulatory T cells of patients with head and neck cancer. Clin. Cancer Res. 15, 6348-6357.
79. Martin, M., Lefaix, J., and Delanian, S. (2000). TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int. J. Radiat. Oncol. Biol. Phys. 47, 277-290.
80. Matsumura, S., Wang, B., Kawashima, N., Braunstein, S., Badura, M., Cameron, T. O., Babb, J. S., Schneider, R. J., Formenti, S. C., Dustin, M. L., and Demaria, S. (2008). Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J. Immunol. 181, 3099-3107.
81. Matzinger, P. (2002). The danger model: a renewed sense of self. Science 296, 301-305.
82. McBride, W. H., Chiang, C. S., Olson, J. L., Wang, C. C., Hong, J. H., Pajonk, F., Dougherty, G. J., Iwamoto, K. S., Pervan, M., and Liao, Y. P. (2004). A sense of danger from radiation. Radiat. Res. 162, 1-19.
83. McBride, W. H., and Howie, S. E. (1986). Induction of tolerance to a murine fibrosarcoma in two zones of dosage-the involvement of suppressor cells. Br. J. Cancer 53, 707-711.
84. McInnes, N., Sadlon, T. J., Brown, C. Y., Pederson, S., Beyer, M., Schultze, J. L., McColl, S., Goodall, G. J., and Barry, S. C. (2012). FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells. Oncogene 31, 1045-1054.
85. Medzhitov, R., Preston-Hurlburt, P., and Janeway, C. A. Jr. (1997). A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397.
86. Mellman, I., Coukos, G., and Dranoff, G. (2011). Cancer immunotherapy comes of age. Nature 480, 480-489.
87. Meylan, E., Tschopp, J., and Karin, M. (2006). Intracellular pattern recognition receptors in the host response. Nature 442, 39-44.
88. Miller, A. M., Lundberg, K., Ozenci, V., Banham, A. H., Hellstrom, M., Egevad, L., and Pisa, P. (2006). CD4+CD25 high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J. Immunol. 177, 7398-7405.
89. Morel, A., Fernandez, N., de La Coste, A., Haddada, H., Viguier, M., Polla, B. S., Antoine, B., and Kahn, A. (1998). Gamma-ray irradiation induces B7.1 costimulatory molecule neoexpression in various murine tumor cells. Cancer Immunol. Immunother. 46, 277-282.
90. Mucida, D., Kutchukhidze, N., Erazo, A., Russo, M., Lafaille, J. J., and Curotto de Lafaille, M. A. (2005). Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Invest. 115, 1923-1933.
91. Nakatsukasa, H., Tsukimoto, M., Tokunaga, A., and Kojima, S. (2010). Repeated gamma irradiation attenuates collagen-induced arthritis via up-regulation of regulatory T cells but not by damaging lymphocytes directly. Radiat. Res. 174, 313-324.
92. Nesslinger, N. J., Sahota, R. A., Stone, B., Johnson, K., Chima, N., King, C., Rasmussen, D., Bishop, D., Rennie, P. S., Gleave, M., Blood, P., Pai, H., Ludgate, C., and Nelson, B. H. (2007). Standard treatments induce antigen-specific immune responses in prostate cancer. Clin. Cancer Res. 13, 1493-1502.
93. North, R. J. (1986). Radiation-induced, immunologically mediated regression of an established tumor as an example of successful therapeutic immunomanipulation. Preferential elimination of suppressor T cells allows sustained production of effector T cells. J. Exp. Med. 164, 1652-1666.
94. O'Day, S. J., Hamid, O., and Urba, W. J. (2007). Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer 110, 2614-2627.
95. Pages, F., Galon, J., Dieu-Nosjean, M. C., Tartour, E., Sautes-Fridman, C., and Fridman, W. H. (2010). Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29, 1093-1102.
96. Penel, N., Adenis, A., and Bocci, G. (2012). Cyclophosphamide-based metronomic chemotherapy: after 10 years of experience, where do we stand and where are we going? Crit. Rev. Oncol. Hematol. 82, 40-50.
97. Perez, C. A., Fu, A., Onishko, H., Hallahan, D. E., and Geng, L. (2009). Radiation induces an antitumour immune response to mouse melanoma. Int. J. Radiat. Biol. 85, 1126-1136.
98. Peterson, R. A. (2012). Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression. Toxicol. Pathol. 40, 186-204.
99. Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., Morton, K. E., Mavroukakis, S. A., Duray, P. H., Steinberg, S. M., Allison, J. P., Davis, T. A., and Rosenberg, S. A. (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.
100. Pillai, M. R., Collison, L. W., Wang, X., Finkelstein, D., Rehg, J. E., Boyd, K., Szymczak-Workman, A. L., Doggett, T., Griffith, T. S., Ferguson, T. A., and Vignali, D. A. (2011). The plasticity of regulatory T cell function. J. Immunol. 187, 4987-4997.
101. Pospisil, M., Hofer, M., Netikova, J., Pipalova, I., Vacek, A., Bartonickova, A., and Volenec, K. (1993). Elevation of extracellular adenosine induces radioprotective effects in mice. Radiat. Res. 134, 323-330.
102. Pospisil, M., Hofer, M., Znojil, V., Netikova, J., Vacha, J., Hola, J., and Vacek, A. (1998). Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice. Eur. J. Haematol. 60, 172-180.
103. Postow, M. A., Callahan, M. K., Barker, C. A., Yamada, Y., Yuan, J., Kitano, S., Mu, Z., Rasalan, T., Adamow, M., Ritter, E., Sedrak, C., Jungbluth, A. A., Chua, R., Yang, A. S., Roman, R. A., Rosner, S., Benson, B., Allison, J. P., Lesokhin, A. M., Gnjatic, S., and Wolchok, J. D. (2012). Immunologic correlates of the abscopal effect in a patient with melanoma. N. Engl. J. Med. 366, 925-931.
104. Qu, Y., Jin, S., Zhang, A., Zhang, B., Shi, X., Wang, J., and Zhao, Y. (2010). Gamma-ray resistance of regulatory CD4+CD25+Foxp3+ T cells in mice. Radiat. Res. 173, 148-157.
105. Rasku, M. A., Clem, A. L., Telang, S., Taft, B., Gettings, K., Gragg, H., Cramer, D., Lear, S. C., McMasters, K. M., Miller, D. M., and Chesney, J. (2008). Transient T cell depletion causes regression of melanoma metastases. J. Transl. Med. 6, 12.
106. Reits, E. A., Hodge, J. W., Herberts, C. A., Groothuis, T. A., Chakraborty, M., Wansley, E. K., Camphausen, K., Luiten, R. M., de Ru, A. H., Neijssen, J., Griekspoor, A., Mesman, E., Verreck, F. A., Spits, H., Schlom, J., van Veelen, P., and Neefjes, J. J. (2006). Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med. 203, 1259-1271.
107. Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., and Karin, M. (2008). NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453, 807-811.
108. Robinson, M. J., Sancho, D., Slack, E. C., LeibundGut-Landmann, S., and Reise Sousa, C. (2006). Myeloid C-type lectins in innate immunity. Nat. Immunol. 7, 1258-1265.
109. Rosenblum, M. D., Gratz, I. K., Paw, J. S., Lee, K., Marshak-Rothstein, A., and Abbas, A. K. (2011). Response to self antigen imprints regulatory memory in tissues. Nature 480, 538-542.
110. Roses, R. E., Xu, M., Koski, G. K., and Czerniecki, B. J. (2008). Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer. Oncogene 27, 200-207.
111. Sakaguchi, N., Miyai, K., and Sakaguchi, S. (1994). Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells. J. Immunol. 152, 2586-2595.
112. 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.
113. 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.
114. Santin, A. D., Hiserodt, J. C., Fruehauf, J., DiSaia, P. J., Pecorelli, S., and Granger, G. A. (1996). Effects of irradiation on the expression of surface antigens in human ovarian cancer. Gynecol. Oncol. 60, 468-474.
115. Sato, Y., Goto, Y., Narita, N., and Hoon, D. S. (2009). Cancer cells expressing toll-like receptors and the tumor microenvironment. Cancer Microenviron. 2(Suppl. 1), 205-214.
116. Schaue, D., Comin-Anduix, B., Ribas, A., Zhang, L., Goodglick, L., Sayre, J. W., Debucquoy, A., Haustermans, K., and McBride, W. H. (2008). T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin. Cancer Res. 14, 4883-4890.
117. Schaue, D., Kachikwu, E. L., and McBride, W. H. (in press). Cytokines in radiobiological responses: a review. Radiat. Res.
118. Schaue, D., and McBride, W. H. (2010). Links between innate immunity and normal tissue radiobiology. Radiat. Res. 173, 406-417.
119. Schaue, D., Ratikan, J. A., Iwamoto, K. S., and McBride, W. H. (2012). Maximizing tumor immunity with fractionated radiation. Int. J. Radiat. Oncol. Biol. Phys. 83, 1306-1310.
120. Seo, A., Ishikawa, F., Nakano, H., Nakazaki, H., Kobayashi, K., and Kakiuchi, T. (1999). Enhancement of B7-1 (CD80) expression on B-lymphoma cells by irradiation. Immunology 96, 642-648.
121. Shevach, E. M. (2004). Regulatory/suppressor T cells in health and disease. Arthritis Rheum. 50, 2721-2724.
122. Shevach, E. M. (2009). Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30, 636-645.
123. Shi, Y., Evans, J. E., and Rock, K. L. (2003). Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425, 516-521.
124. Sitkovsky, M. V. (2009). T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response. Trends Immunol. 30, 102-108.
125. Spanos, W. C., Nowicki, P., Lee, D. W., Hoover, A., Hostager, B., Gupta, A., Anderson, M. E., and Lee, J. H. (2009). Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch. Otolaryngol. Head Neck Surg. 135, 1137-1146.
126. Stamell, E. F., Wolchok, J. D., Gnjatic, S., Lee, N. Y., and Brownell, I. (2012). The abscopal effect associated with a systemic anti-melanoma immune response. Int. J. Radiat. Oncol. Biol. Phys.
127. Steinman, R. M., Hawiger, D., and Nussenzweig, M. C. (2003). Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685-711.
128. Takahashi, H., Kanno, T., Nakayamada, S., Hirahara, K., Sciume, G., Muljo, S. A., Kuchen, S., Casellas, R., Wei, L., Kanno, Y., and O'Shea, J. J. (2012). TGF-beta and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat. Immunol. 13, 587-595.
129. Tang, S., Moore, M. L., Grayson, J. M., and Dubey, P. (2012). Increased CD8+ T-cell function following castration and immunization is countered by parallel expansion of regulatory T cells. Cancer Res. 72, 1975-1985.
130. Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., and Shevach, E. M. (2010). Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433-3441.
131. Tilkin, A. F., Schaaf-Lafontaine, N., Van Acker, A., Boccadoro, M., and Urbain, J. (1981). Reduced tumor growth after low-dose irradiation or immunization against blastic suppressor T cells. Proc. Natl. Acad. Sci. U.S.A. 78, 1809-1812.
132. Tyurina, Y. Y., Tyurin, V. A., Kapralova, V. I., Wasserloos, K., Mosher, M., Epperly, M. W., Greenberger, J. S., Pitt, B. R., and Kagan, V. E. (2011). Oxidative lipidomics of gamma-radiation-induced lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. Radiat. Res. 175, 610-621.
133. Ullrich, E., Bonmort, M., Mignot, G., Kroemer, G., and Zitvogel, L. (2008). Tumor stress, cell death and the ensuing immune response. Cell Death Differ. 15, 21-28.
134. Van Ginderachter, J. A., Movahedi, K., Hassanzadeh Ghassabeh, G., Meerschaut, S., Beschin, A., Raes, G., and De Baetselier, P. (2006). Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology 211, 487-501.
135. Vincent, J., Mignot, G., Chalmin, F., Ladoire, S., Bruchard, M., Chevriaux, A., Martin, F., Apetoh, L., Rebe, C., and Ghiringhelli, F. (2010). 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 70, 3052-3061.
136. von Boehmer, H. (2005). Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6, 338-344.
137. Waite, J. C., and Skokos, D. (2012). Th17 response and inflammatory autoimmune diseases. Int. J. Inflamm. 2012, 819467.
138. Walker, L. S. (2004). CD4+ CD25+ Treg: divide and rule? Immunology 111, 129-137.
139. Weber, J., Thompson, J. A., Hamid, O., Minor, D., Amin, A., Ron, I., Ridolfi, R., Assi, H., Maraveyas, A., Berman, D., Siegel, J., and O'Day, S. J. (2009). A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin. Cancer Res. 15, 5591-5598.
140. Weng, L., Williams, R. O., Vieira, P. L., Screaton, G., Feldmann, M., and Dazzi, F. (2010). The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity. Ann. Rheum. Dis. 69, 1519-1526.
141. Whiteside, T. L. (2009). Tricks tumors use to escape from immune control. Oral Oncol. 45, e119-e123.
142. Xu, L., Kitani, A., Fuss, I., and Strober, W. (2007). Cutting edge: regulatory T cells induce CD4+CD25-Foxp3-T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J. Immunol. 178, 6725-6729.
143. Yang, J. C., Hughes, M., Kammula, U., Royal, R., Sherry, R. M., Topalian, S. L., Suri, K. B., Levy, C., Allen, T., Mavroukakis, S., Lowy, I., White, D. E., and Rosenberg, S. A. (2007). Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J. Immunother. 30, 825-830.
144. Zarek, P. E., Huang, C. T., Lutz, E. R., Kowalski, J., Horton, M. R., Linden, J., Drake, C. G., and Powell, J. D. (2008). A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 111, 251-259.
145. Zheng, S. G., Wang, J., and Horwitz, D. A. (2008). Cutting edge: Foxp3+CD4+CD25+ regulatory T cells induced by IL-2 and TGF-beta are resistant to Th17 conversion by IL-6. J. Immunol. 180, 7112-7116.
146. Zhu, J., and Paul, W. E. (2010). Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol. Rev. 238, 247-262.
147. Zitvogel, L., Tesniere, A., and Kroemer, G. (2006). Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat. Rev. Immunol. 6, 715-727.