The effect of ionizing radiation on regulatory T cells in health and disease

Cancer Letters

Volumn 368, Issue 2, 2015, Pages 252-261

  Persa, Eszter ^a   Balogh, Andrea ^a   Sáfrány, Géza ^a   Lumniczky, Katalin ^a  

^a National Research Institute for Radiobiology and Radiohygiene Budapest   (Hungary)

Author keywords

Immune therapy; Radiotherapy; Regulatory T cells; Tumor

Indexed keywords

APOPTOSIS; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CELL PROLIFERATION; HUMAN; IMMUNOREGULATION; IONIZING RADIATION; IRRADIATION; LYMPHOCYTE SUBPOPULATION; LYMPHOCYTIC INFILTRATION; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PHENOTYPE; PREDICTIVE VALUE; PRIORITY JOURNAL; RADIATION RESPONSE; RADIOSENSITIVITY; REGULATORY T LYMPHOCYTE; SHORT SURVEY; ANIMAL; IMMUNOLOGY; NEOPLASMS;

ANIMALS; HUMANS; NEOPLASMS; T-LYMPHOCYTES, REGULATORY;

EID: 84941877287     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2015.03.003     Document Type: Review

References (143)

1. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. 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 1995, 155:1151-1164.
2. Dieckmann D., Plottner H., Berchtold S., Berger T., Schuler G. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J. Exp. Med 2001, 193:1303-1310.
3. Banerjee A., Vasanthakumar A., Grigoriadis G. Modulating T regulatory cells in cancer: how close are we?. Immunol. Cell Biol 2013, 91:340-349.
4. Jordan M.S., Boesteanu A., Reed A.J., Petrone A.L., Holenbeck A.E., Lerman M.A., et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol 2001, 2:301-306.
5. Itoh M., Takahashi T., Sakaguchi N., Kuniyasu Y., Shimizu J., Otsuka F., et al. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol 1999, 162:5317-5326.
6. Deaglio S., Dwyer K.M., Gao W., Friedman D., Usheva A., Erat A., et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med 2007, 204:1257-1265.
7. Bilate A.M., Lafaille J.J. Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu. Rev. Immunol 2012, 30:733-758.
8. Thornton A.M., Korty P.E., Tran D.Q., Wohlfert E.A., Murray P.E., Belkaid Y., et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol 2010, 184:3433-3441.
9. Gottschalk R.A., Corse E., Allison J.P. Expression of Helios in peripherally induced Foxp3+ regulatory T cells. J. Immunol 2012, 188:976-980.
10. Huehn J., Siegmund K., Lehmann J.C., Siewert C., Haubold U., Feuerer M., et al. Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J. Exp. Med 2004, 199:303-313.
11. Belkaid Y., Piccirillo C.A., Mendez S., Shevach E.M., Sacks D.L. CD4CD25 regulatory T cells control Leishmania major persistence and immunity. Nature 2002, 420:502-507.
12. Min B., Thornton A., Caucheteux S.M., Younes S.A., Oh K., Hu-Li J., et al. Gut flora antigens are not important in the maintenance of regulatory T cell heterogeneity and homeostasis. Eur. J. Immunol 2007, 37:1916-1923.
13. Asseman C., Mauze S., Leach M.W., Coffman R.L., Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med 1999, 190:995-1004.
14. Wing K., Onishi Y., Prieto-Martin P., Yamaguchi T., Miyara M., Fehervari Z., et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008, 322:271-275.
15. McHugh R.S., Whitters M.J., Piccirillo C.A., Young D.A., Shevach E.M., Collins M., et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002, 16:311-323.
16. Nocentini G., Ronchetti S., Cuzzocrea S., Riccardi C. GITR/GITRL: more than an effector T cell co-stimulatory system. Eur. J. Immunol 2007, 37:1165-1169.
17. Tran D.Q., Andersson J., Wang R., Ramsey H., Unutmaz D., Shevach E.M. GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. PNAS 2009, 106:13445-13450.
18. Edwards J.P., Fujii H., Zhou A.X., Creemers J., Unutmaz D., Shevach E.M. Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J. Immunol 2013, 190:5506-5515.
19. Yan L., Silva D.M., Verma B., Gray A., Brand H.E., Skeate J.G., et al. Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes. Prostate 2015, 75:280-291.
20. Favaloro J., Brown R., Aklilu E., Yang S., Suen H., Hart D., et al. Myeloma skews regulatory T and pro-inflammatory T helper 17 cell balance in favor of a suppressive state. Leuk. Lymphoma 2014, 55:1090-1098.
21. Drennan S., Stafford N.D., Greenman J., Green V.L. Increased frequency and suppressive activity of CD127 (low/-) regulatory T cells in the peripheral circulation of patients with head and neck squamous cell carcinoma are associated with advanced stage and nodal involvement. Immunology 2013, 140:335-343.
22. Wu H., Chen P., Liao R., Li Y.W., Yi Y., Wang J.X., et al. Intratumoral regulatory T cells with higher prevalence and more suppressive activity in hepatocellular carcinoma patients. J. Gastroenterol. Hepatol 2013, 28:1555-1564.
23. Watanabe M.A., Oda J.M., Amarante M.K., Cesar Voltarelli J. Regulatory T cells and breast cancer: implications for immunopathogenesis. Cancer Metastasis Rev 2010, 29:569-579.
24. Grauer O.M., Nierkens S., Bennink E., Toonen L.W., Boon L., Wesseling P., et al. CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int. J. Cancer 2007, 121:95-105.
25. Gasparoto T.H., de Souza Malaspina T.S., Benevides L., de Melo E.J., Costa M.R., Damante J.H., et al. Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment. Cancer Immunol. Immunother 2010, 59:819-828.
26. Szczepanski M.J., Szajnik M., Czystowska M., Mandapathil M., Strauss L., Welsh A., et al. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin. Cancer Res 2009, 15:3325-3332.
27. Griffiths R.W., Elkord E., Gilham D.E., Ramani V., Clarke N., Stern P.L., et al. Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival. Cancer Immunol. Immunother 2007, 56:1743-1753.
28. Curiel T.J., Coukos G., Zou L., Alvarez X., Cheng P., Mottram P., et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med 2004, 10:942-949.
29. Maruyama K., Motoyama S., Anbai A., Usami S., Sato Y., Shibuya K., et al. Therapeutic strategy for the treatment of postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy of radiotherapy. Dis. Esophagus 2011, 24:166-171.
30. Ishida T., Ishii T., Inagaki A., Yano H., Komatsu H., Iida S., et al. Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 2006, 66:5716-5722.
31. Chang D.K., Sui J., Geng S., Muvaffak A., Bai M., Fuhlbrigge R.C., et al. Humanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells and abrogates suppression by T-regulatory cells. Mol. Cancer Ther 2012, 11:2451-2461.
32. Gobert M., Treilleux I., Bendriss-Vermare N., Bachelot T., Goddard-Leon S., Arfi V., et al. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res 2009, 69:2000-2009.
33. Li Y.Q., Liu F.F., Zhang X.M., Guo X.J., Ren M.J., Fu L. Tumor secretion of CCL22 activates intratumoral Treg infiltration and is independent prognostic predictor of breast cancer. PLoS ONE 2013, 8. e76379.
34. Schott A.K., Pries R., Wollenberg B. Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer. Int. J. Mol. Med 2010, 26:67-75.
35. Mizukami Y., Kono K., Kawaguchi Y., Akaike H., Kamimura K., Sugai H., et al. CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int. J. Cancer 2008, 122:2286-2293.
36. Jacobs J.F., Idema A.J., Bol K.F., Grotenhuis J.A., de Vries I.J., Wesseling P., et al. Prognostic significance and mechanism of Treg infiltration in human brain tumors. J. Neuroimmunol 2010, 225:195-199.
37. Schlecker E., Stojanovic A., Eisen C., Quack C., Falk C.S., Umansky V., et al. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth. J. Immunol 2012, 189:5602-5611.
38. Ward S.T., Li K.K., Hepburn E., Weston C.J., Curbishley S.M., Reynolds G.M., et al. The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer. Br. J. Cancer 2015, 112:319-328.
39. Chen K.J., Lin S.Z., Zhou L., Xie H.Y., Zhou W.H., Taki-Eldin A., et al. Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS ONE 2011, 6. e24671.
40. Liu J., Zhang N., Li Q., Zhang W., Ke F., Leng Q., et al. Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS ONE 2011, 6. e19495.
41. Ondondo B., Jones E., Godkin A., Gallimore A. Home sweet home: the tumor microenvironment as a haven for regulatory T cells. Front. Immunol 2013, 4:197.
42. Chen W., Jin W., Hardegen N., Lei K.J., Li L., Marinos N., et al. 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 2003, 198:1875-1886.
43. Liu V.C., Wong L.Y., Jang T., Shah A.H., Park I., Yang X., et al. Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J. Immunol 2007, 178:2883-2892.
44. Oleinika K., Nibbs R.J., Graham G.J., Fraser A.R. Suppression, subversion and escape: the role of regulatory T cells in cancer progression. Clin. Exp. Immunol 2013, 171:36-45.
45. Zhou G., Levitsky H.I. Natural regulatory T cells and de novo induced regulatory T cells contribute independently to tumor-specific tolerance. J. Immunol 2007, 178:2155-2162.
46. Elkord E., Sharma S., Burt D.J., Hawkins R.E. Expanded subpopulation of FoxP3+ T regulatory cells in renal cell carcinoma co-express Helios, indicating they could be derived from natural but not induced Tregs. Clin. Immunol 2011, 140:218-222.
47. Zhou G., Drake C.G., Levitsky H.I. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 2006, 107:628-636.
48. Ahmadzadeh M., Rosenberg S.T. IL-2 administration increases CD4(+)CD25(hi) Foxp3(+) regulatory T cells in cancer patients. Blood 2006, 107:2409-2414.
49. Jensen H.K., Donskov F., Nordsmark M., Marcussen N., von der Maase H. Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma. Clin. Cancer Res 2009, 15:1052-1058.
50. Wainwright D.A., Sengupta S., Han Y., Lesniak M.S. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro-Oncol 2011, 13:1308-1323.
51. Wolf A.M., Wolf D., Steurer M., Gastl G., Gunsilius E., Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin. Cancer Res 2003, 9:606-612.
52. Lim K.P., Chun N.A., Ismail S.M., Abraham M.T., Yusoff M.N., Zain R.B., et al. CD4+CD25hiCD127low regulatory T cells are increased in oral squamous cell carcinoma patients. PLoS ONE 2014, 9. e103975.
53. Ichihara F., Kono K., Takahashi A., Kawaida H., Sugai H., Fujii H. Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patient with gastric and esophageal cancers. Clin. Cancer Res 2003, 9:4404-4408.
54. Ormandy L.A., Hillemann T., Wedemeyer H., Manns M.P., Greten T.F., Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res 2005, 65:2457-2464.
55. Liyanage U.K., Moore T.T., Joo H.G., Tanaka Y., Herrmann V., Doherty G., et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol 2002, 169:2756-2761.
56. Kono K., Kawaida H., Takahashi A., Sugai H., Mimura K., Miyagawa N., et al. CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol. Immunother 2006, 55:1064-1071.
57. Wang Y., Ma Y., Fang Y., Wu S., Liu L., Fu D., et al. Regulatory T cell: a protection for tumour cells. J. Cell. Mol. Med 2012, 16:425-436.
58. Pandiyan P., Zheng L., Ishihara S., Reed J., Lenardo M.J. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat. Immunol 2007, 8:1353-1362.
59. Govindaraj C., Scalzo-Inguanti K., Madondo M., Hallo J., Flanagan K., Quinn M., et al. Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs within the tumor microenvironment. Clin. Immunol 2013, 149:97-110.
60. Kalathil S., Lugade A.A., Miller A., Iyer R., Thanavala Y. Higher frequencies of GARP(+)CTLA-4(+)Foxp3(+) T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality. Cancer Res 2013, 73:2435-2444.
61. Ghiringhelli F., Ménard C., Terme M., Flament C., Taieb J., Chaput N., et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J. Exp. Med 2005, 202:1075-1085.
62. Chung D.J., Rossi M., Romano E., Ghith J., Yuan J., Munn D.H., et al. Indoleamine2,3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells. Blood 2009, 114:555-563.
63. Anderson B.E., McNiff J.M., Matte C., Athanasiadis I., Shlomchik W.D., Shlomchik M.J. Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease. Blood 2004, 104:1565-1573.
64. Komatsu N., Hori S. Full restoration of peripheral Foxp3+ regulatory T cell pool by radioresistant host cells in scurfy bone marrow chimeras. PNAS 2007, 104:8959-8964.
65. Qu Y., Jin S., Zhang A., Zhang B., Shi X., Wang J., et al. Gamma-ray resistance of regulatory CD4+CD25+Foxp3+ T cells in mice. Radiat. Res 2010, 173:148-157.
66. Qu Y., Zhang B., Liu S., Zhang A., Wu T., Zhao Y. 2-Gy whole-body irradiation significantly alters the balance of CD4+ CD25- T effector cells and CD4+ CD25+ Foxp3+ T regulatory cells in mice. Cell. Mol. Immunol 2010, 7:419-427.
67. Balogh A., Persa E., Bogdándi E.N., Benedek A., Hegyesi H., Sáfrány G., et al. The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells. Inflamm. Res 2013, 62:201-212.
68. McFarland H.I., Puig M., Grajkowska L.T., Tsuji K., Lee J.P., Mason K.P., et al. Regulatory T cells in γ irradiation-induced immune suppression. PLoS ONE 2012, 7. e39092.
69. Bogdándi E.N., Balogh A., Felgyinszki N., Szatmári T., Persa E., Hildebrandt G., et al. Effects of low-dose radiation on the immune system of mice after total-body irradiation. Radiat. Res 2010, 174:480-489.
70. Schaue D., Ratikan J.A., Iwamoto K.S., McBride W.H. Maximizing tumor immunity with fractionated radiation. Int. J. Radiat. Oncol. Biol. Phys 2012, 83:1306-1310.
71. Winzler C., Fantinato M., Giordan M., Calore E., Basso G., Messina C. CD4+ regulatory cells are more resistant to DNA damage compared to CD4+ T effector cells as revealed by flow cytometric analysis. Cytometry 2011, 79A:903-911.
72. Baba J., Watanabe S., Saida Y., Tanaka T., Miyabayashi T., Koshio J., et al. Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia. Blood 2012, 120:2417-2427.
73. Mougiakakos D., Johansson C.C., Kiessling R. Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death. Blood 2009, 113:3542-3545.
74. Baria K., Warren C., Roberts S.A., West C.M., Scott D. Chromosomal radiosensitivity as a marker of predisposition to common cancers?. Br. J. Cancer 2001, 84:892-896.
75. Terzoudi G.I., Hatzi V.I., Barszczewska K., Manola K.N., Stavropoulou C., Angelakis P., et al. G2-checkpoint abrogation in irradiated lymphocytes: a new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer. Int. J. Oncol 2009, 35:1223-1230.
76. Pantelias G.E., Terzoudi G.I. A standardized G2-assay for the prediction of individual radiosensitivity. Radiother. Oncol 2011, 101:28-34.
77. Suffner J., Hochweller K., Kühnle M.C., Li X., Kroczek R.A., Garbi N., et al. Dendritic cells support homeostatic expansion of Foxp3+ regulatory T cells in Foxp3.LuciDTR mice. J. Immunol 2010, 184:1810-1820.
78. Curotto de Lafaille M.A., Lino A.C., Kutchukhidze N., Lafaille J.J. CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J. Immunol 2004, 173:7259-7268.
79. Haribhai D., Lin W., Edwards B., Ziegelbauer J., Salzman N.H., Carlson M.R., et al. A central role for induced regulatory T cells in tolerance induction in experimental colitis. J. Immunol 2009, 182:3461-3468.
80. Barcellos-Hoff M.H., Derynck R., Tsang M.L., Weatherbee J.A. Transforming growth factor-β activation in irradiated murine mammary gland. J. Clin. Invest 1994, 93:892-899.
81. Gao L., Li F.S., Chen X.H., Liu Q.W., Feng J.B., Liu Q.J., et al. Radiation induces phosphorylation of STAT3 in a dose- and time-dependent manner. Asian Pac. J. Cancer Prev 2014, 15:6161-6164.
82. Laurence A., Amarnath S., Mariotti J., Kim Y.C., Foley J., Eckhaus M., et al. STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease. Immunity 2012, 37:209-222.
83. Fujino M., Li X.K. Role of STAT3 in regulatory T lymphocyte plasticity during acute graft-vs.-host-disease,. JAKSTAT 2013, 2. e24529.
84. Cao M., Cabrera R., Xu Y., Liu C., Nelson D. Gamma irradiation alters the phenotype and function of CD4+CD25+ regulatory T cells. Cell Biol. Int 2009, 33:565-571.
85. Billiard F., Buard V., Benderitter M., Linard C. Abdominal γ-radiation induces an accumulation of function-impaired regulatory T cells in the small intestine. Int. J. Radiat. Oncol. Biol. Phys 2011, 80:869-876.
86. Park B.S., Hong G.U., Ro J.Y. Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice. Radiat. Res 2013, 179:570-583.
87. Nakatsukasa H., Tsukimoto M., Tokunaga A., Kojima S. Repeated gamma irradiation attenuates collagen-induced arthritis via up-regulation of regulatory T cells but not by damaging lymphocytes directly. Radiat. Res 2010, 174:313-324.
88. Weng L., Williams R.O., Vieira P.L., Screaton G., Feldmann M., Dazzi F. The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity. Ann. Rheum. Dis 2010, 69:1519-1526.
89. Tsukimoto M., Nakatsukasa H., Sugawara K., Yamashita K., Kojima S. Repeated 0.5-Gy gamma irradiation attenuates experimental autoimmune encephalomyelitis with up-regulation of regulatory T cells and suppression of IL17 production. Radiat. Res 2008, 170:429-436.
90. Dong J.C., Cheng G.H., Shan Y.X., Wu N., Shao M.L., Li P.W., et al. Role of PLC-PIP2 and cAMP-PKA signal pathways in radiation-induced immune-suppressing effect. Biomed. Environ. Sci 2014, 27:27-34.
91. An Y.S., Kim M.R., Lee S.S., Lee Y.S., Chung E., Song J.Y., et al. TGF-β signaling plays an important role in resisting γ-irradiation. Exp. Cell Res 2013, 319:466-473.
92. Wu C.T., Hsieh C.C., Yen T.C., Chen W.C., Chen M.F. TGF-β1 mediates the radiation response of prostate cancer. J. Mol. Med 2015, 93:73-82.
93. Kim M.R., Lee J., An Y.S., Jin Y.B., Park I.C., Chung E., et al. TGFβ1 Protects cells from γ-IR by enhancing the activity of the NHEJ repair pathway. Mol. Cancer Res 2015, 13:319-329.
94. Chatzinikolaou G., Karakasilioti I., Garinis G.A. DNA damage and innate immunity: links and trade-offs. Trends Immunol 2014, 35:429-435.
95. Sprung C.N., Ivashkevich A., Forrester H.B., Redon C.E., Georgakilas A., Martin O.A. Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects. Cancer Lett 2015, 356:72-78.
96. Wild C.A., Brandau S., Lindemann M., Lotfi R., Hoffmann T.K., Lang S., et al. Toll-like receptors in regulatory T cells of patients with head and neck cancer. Arch. Otolaryngol. Head Neck Surg 2010, 136:1253-1259.
97. Hellweg C.E. The nuclear factor κB pathway: a link to the immune system in the radiation response. Cancer Lett 2015, pii: S0304-3835(15)00122-6. 10.1016/j.canlet.2015.02.019.
98. Luo Y., Boyle D.L., Hammaker D., Edgar M., Franzoso G., Firestein G.S. Suppression of collagen-induced arthritis in growth arrest and DNA damage inducible 45β (Gadd45β)-deficient mice. Arthritis Rheum 2011, 63:2949-2955.
99. Salvador J.M., Brown-Clay J.D., Fornace A.J. Gadd45 in stress signaling, cell cycle control, and apoptosis. Adv. Exp. Med. Biol 2013, 793:1-19.
100. Lumniczky K., Sáfrány G. The impact of radiation therapy on the antitumor immunity: local effects and systemic consequences. Cancer Lett 2015, 356:114-125.
101. Schuler P.J., Harasymczuk M., Schilling B., Saze Z., Strauss L., Lang S., et al. Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer. Clin. Cancer Res 2013, 19:6585-6596.
102. Qinfeng S., Depu W., Xiaofeng Y., Shah W., Hongwei C., Yili W. In situ observation of the effects of local irradiation on cytotoxic and regulatory T lymphocytes in cervical cancer tissue. Radiat. Res 2013, 179:584-589.
103. Battaglia A., Buzzonetti A., Martinelli E., Fanelli M., Petrillo M., Ferrandina G., et al. Selective changes in the immune profile of tumor-draining lymph nodes after different neoadjuvant chemoradiation regimens for locally advanced cervical cancer. Int. J. Radiat. Oncol. Biol. Phys 2010, 76:1546-1553.
104. Fadul C.E., Fisher J.L., Gui J., Hampton T.H., Côté A.L., Ernstoff M.S. Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme. Neuro-Oncol 2011, 13:393-400.
105. Schaue D., Xie M.W., Ratikan J.A., McBride W.H. RegulatoryT cells in radiotherapeutic responses. Front. Oncol 2012, 2:90.
106. Sekar D., Hahn C., Brüne B., Roberts E., Weigert A. Apoptotic tumor cells induce IL-27 release from human DCs to activate Treg cells that express CD69 and attenuate cytotoxicity. Eur. J. Immunol 2012, 42:1585-1598.
107. Li C.G., He M.R., Wu F.L., Li Y.J., Sun A. Akt promotes irradiation-induced regulatory T-cell survival in hepatocellular carcinoma. Am. J. Med. Sci 2013, 346:123-127.
108. Wang M., Gou X., Wang L. Protein kinase B promotes radiation-induced regulatory T cell survival in bladder carcinoma. Scand. J. Immunol 2012, 76:70-74.
109. Ko A., Kanehisa A., Martins I., Senovilla L., Chargari C., Dugue D., et al. Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signaling. Cell Death Differ 2014, 21:92-99.
110. Wrzesinski C., Paulos C.M., Kaiser A., Muranski P., Palmer D.C., Gattinoni L., et al. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J. Immunother 2010, 33:1-7.
111. Yao X., Ahmadzadeh M., Lu Y.C., Liewehr D.J., Dudley M.E., Liu F., et al. Levels of peripheral CD4(+)FoxP3(+) regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer. Blood 2012, 119:5688-5696.
112. Quezada S.A., Simpson T.R., Peggs K.S., Merghoub T., Vider J., Fan X., et al. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med 2010, 207:637-650.
113. Radojcic V., Bezak K.B., Skarica M., Pletneva M.A., Yoshimura K., Schulick R.D., et al. Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination. Cancer Immunol. Immunother 2010, 59:137-148.
114. Tsuchikawa T., Hirano S., Tanaka E., Matsumoto J., Kato K., Nakamura T., et al. Novel aspects of preoperative chemoradiation therapy improving anti-tumor immunity in pancreatic cancer. Cancer Sci 2013, 104:531-535.
115. Vizio B., Novarino A., Giacobino A., Cristiano C., Prati A., Ciuffreda L., et al. Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome. Exp. Ther. Med 2012, 4:70-78.
116. Son C.H., Shin D.Y., Kim S.D., Park H.S., Jung M.H., Bae J.H., et al. Improvement of antitumor effect of intratumoral injection of immature dendritic cells into irradiated tumor by cyclophosphamide in mouse colon cancer model. J. Immunother 2012, 35:607-614.
117. Tabachnyk M., Distel L.V., Büttner M., Grabenbauer G.G., Nkenke E., Fietkau R., et al. Radiochemotherapy induces a favourable tumour infiltrating inflammatory cell profile in head and neck cancer. Oral Oncol 2012, 48:594-601.
118. Wei S., Egenti M.U., Teitz-Tennenbaum S., Zou W., Chang A.E. Effects of tumor irradiation on host T-regulatory cells and systemic immunity in the context of adoptive T-cell therapy in mice. J. Immunother 2013, 36:124-132.
119. Hurwitz A.A., Yu T.F.Y., Leach D.R., Allison J.P. CTLA-4 blockade synergize with tumor-derived granulocyte-macrophage colony stimulating-factor for treatment of an experimental mammary carcinoma. PNAS 1998, 95:10067-10071.
120. Demaria S., Kawashima N., Yang A.M., Devitt M.L., Babb J.S., Allison J.P., et al. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin. Cancer Res 2005, 11:728-734.
121. Silk A.W., Bassetti M.F., West B.T., Tsien C.I., Lao C.D. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med 2013, 2:899-906.
122. Barker C.A., Postow M.A. Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int. J. Radiat. Oncol. Biol. Phys 2014, 88:986-997.
123. Grimaldi A.M., Simeone E., Giannarelli D., Muto P., Falivene S., Borzillo V., et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology 2014, 3. e28780.
124. Golden E.B., Demaria S., Schiff P.B., Chachoua A., Formenti S.C. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol. Res 2013, 1:365-372.
125. Demaria S., Pilones K.A., Formenti S.C., Dustin M.L. Exploiting the stress response to radiation to sensitize poorly immunogenic tumors to anti-CTLA-4 treatment. Oncoimmunology 2013, 2. e23127.
126. Slovin S.F., Higano C.S., Hamid O., Tejwani S., Harzstark A., Alumkal J.J., et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann. Oncol 2013, 24:1813-1821.
127. Kwon E.D., Drake C.G., Scher H.I., Fizazi K., Bossi A., van den Eertwegh A.J., et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2014, 15:700-712.
128. Son C.H., Bae J.H., Shin D.Y., Lee H.R., Choi Y.J., Jo W.S., et al. CTLA-4 blockade enhances antitumor immunity of intratumoral injection of immature dendritic cells into irradiated tumor in a mouse colon cancer model. J. Immunother 2014, 37:1-7.
129. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12:252-264.
130. Hardy B., Indjiia L., Rodionov G., Raiter A., Inbal A. Treatment with BAT monoclonal antibody decreases tumor burden in a murine model of leukemia/lymphoma. Int. J. Oncol 2001, 19:897-902.
131. Feinmesser M., Raiter A., Hardy B. Prevention of melanoma metastases in lungs of BAT treated and peptide immunized mice. Int. J. Oncol 2006, 29:911-917.
132. Hardy B., Morgenstern S., Raiter A., Rodionov G., Fadaeev L., Niv Y. BAT monoclonal antibody immunotherapy of human metastatic colorectal carcinoma in mice. Cancer Lett 2005, 229:217-222.
133. Zheng Z., Wang P., Wang H., Zhang X., Wang M., Cucinotta F.A., et al. Combining heavy ion radiation and artificial microRNAs to target the homologous recombination repair gene efficiently kills human tumor cells. Int. J. Radiat. Oncol. Biol. Phys 2013, 85:466-471.
134. Castro M.G., Baker G.J., Lowenstein P.R. Blocking immunosuppressive checkpoints for glioma therapy: the more the merrier!. Clin. Cancer Res 2014, 20:5147-5149.
135. Lipson E.J. Re-orienting the immune system: durable tumor regression and successful re-induction therapy using anti-PD1 antibodies. Oncoimmunology 2013, 2. e23661.
136. Westin J.R., Chu F., Zhang M., Fayad L.E., Kwak L.W., Fowler N., et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol 2014, 15:69-77.
137. deLeeuw R.J., Kost S.E., Kakal J.A., Nelson B.H. The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. Clin. Cancer Res 2012, 18:3022-3029.
138. Kim K.J., Lee K.S., Cho H.J., Kim Y.H., Yang H.K., Kim W.H., et al. Prognostic implications of tumor-infiltrating FoxP3+ regulatory T cells and CD8+ cytotoxic T cells in microsatellite-unstable gastric cancers. Hum. Pathol 2014, 45:285-293.
139. Näsman A., Romanitan M., Nordfors C., Grün N., Johansson H., Hammarstedt L., et al. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS ONE 2012, 7. e38711.
140. Yue Q., Zhang X., Ye H.X., Wang Y., Du Z.G., Yao Y., et al. The prognostic value of Foxp3+ tumor-infiltrating lymphocytes in patients with glioblastoma. J. Neurooncol 2014, 116:251-259.
141. Whiteside T.L. Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression?. Cancer Immunol. Immunother 2014, 63:67-72.
142. Lissoni P., Brivio F., Fumagalli L., Messina G., Meregalli S., Porro G., et al. Effects of the conventional antitumor therapies surgery, chemotherapy, radiotherapy and immunotherapy on regulatory T lymphocytes in cancer patients. Anticancer Res 2009, 29:1847-1852.
143. Schmidt M.A., Förtsch C., Schmidt M., Rau T.T., Fietkau R., Distel L.V. Circulating regulatory T cells of cancer patients receiving radiochemotherapy may be useful to individualize cancer treatment. Radiother. Oncol 2012, 104:131-138.