Influence of tumors on protective anti-tumor immunity and the effects of irradiation

Frontiers in Oncology

Volumn 3 FEB, Issue , 2013, Pages

  Foulds, Gemma A ^a,b   Radons, Jürgen ^c   Kreuzer, Mira ^a   Multhoff, Gabriele ^b,d   Pockley, Alan G ^e  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c Multimmune GmbH   (Germany)

^d INSTITUTE OF EPIDEMIOLOGY   (Germany)

^e NOTTINGHAM TRENT UNIVERSITY   (United Kingdom)

Author keywords

Immunoregulation; NK cells; T cells; Tumor immunity; Tumor microenvironment

Indexed keywords

BASILIXIMAB; CD134 ANTIGEN; CYCLOPHOSPHAMIDE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACLIZUMAB; DENILEUKIN DIFTITOX; GRANZYME B; INTERLEUKIN 10; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 7 RECEPTOR; IPILIMUMAB; MACROPHAGE DERIVED CHEMOKINE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MDX 100; MONOCYTE CHEMOTACTIC PROTEIN 1; NATURAL KILLER CELL RECEPTOR NKG2D; NEUROPILIN 1; NIVOLUMAB; PERFORIN; PROGRAMMED DEATH 1 RECEPTOR; PROSTAGLANDIN E2; PROTEIN P58; RECOMBINANT INTERLEUKIN 2; SORAFENIB; SUNITINIB; TICILIMUMAB; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 8; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG; YERVOV; ZENAPEX;

ADAPTIVE IMMUNITY; ANTIGEN EXPRESSION; ANTINEOPLASTIC ACTIVITY; ARTHRITIS; CANCER RADIOTHERAPY; CD4+ CD25+ T LYMPHOCYTE; DIARRHEA; HUMAN; HYPOPHYSITIS; IMMUNOREGULATION; INNATE IMMUNITY; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; MELANOMA; NATURAL KILLER CELL; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RASH; REGULATORY T LYMPHOCYTE; REVIEW; T CELL LEUKEMIA; THYROIDITIS; TUMOR IMMUNITY;

EID: 84881525704     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00014     Document Type: Review

References (246)

1. Adotevi, O., Pere, H., Ravel, P., Haicheur, N., Badoual, C., Merillon, N., et al. (2010). A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J. Immunother. 33, 991-998.
2. Algarra, I., Collado, A., and Garrido, F. (1997). Altered MHC class I antigens in tumors. Int. J. Clin. Lab. Res. 27, 95-102.
3. Al Omar, S. Y., Marshall, E., Middleton, D., and Christmas, S. E. (2011). Increased killer immunoglobulin-like receptor expression and functional defects in natural killer cells in lung cancer. Immunology 133, 94-104.
4. + T helper cells and hindered by naturally occurring T regulatory cells. J. Immunol. 174, 2591-2601.
5. Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., et al. (2007). Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13, 1050-1059.
6. + T lymphocytes. I. Inhibition of the IL-2-dependent proliferation by anti-Kp43 monoclonal antibody. J. Immunol. 144, 3238-3247.
7. Asano, M., Toda, M., Sakaguchi, N., and Sakaguchi, S. (1996). Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med. 184, 387-396.
8. Baskic, D., Vujanovic, L., Arsenijevic, N., Whiteside, T. L., Myers, E. N., and Vujanovic, N. L. (2012). Suppression of natural killer-cell and dendritic-cell apoptotic tumoricidal activity in patients with head and neck cancer. Head Neck. doi: 10.1002/hed.22968. [Epub ahead of print].
9. Bausero, M. A., Gastpar, R., Multhoff, G., and Asea, A. (2005). Alternative mechanism by which IFN-γ enhances tumor recognition: active release of heat shock protein 72. J. Immunol. 175, 2900-2912.
10. Benencia, F., Courreges, M. C., Conejo-Garcia, J. R., Mohamed-Hadley, A., Zhang, L., Buckanovich, R. J., et al. (2005). HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer. Mol. Ther. 12, 789-802.
11. Bergmann, C., Strauss, L., Wang, Y., Szczepanski, M. J., Lang, S., Johnson, J. T., et al. (2008). T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin. Cancer Res. 14, 3706-3715.
12. Bergmann, C., Strauss, L., Zeidler, R., Lang, S., and Whiteside, T. L. (2007). Expansion of human T regulatory type 1 cells in the microenvironment of cyclooxygenase 2 overexpressing head and neck squamous cell carcinoma. Cancer Res. 67, 8865-8873.
13. Berman, D., Parker, S. M., Siegel, J., Chasalow, S. D., Weber, J., Galbraith, S., et al. (2010). Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. Cancer Immun. 10, 11.
14. Bernhard, E. J., Kao, G., Cox, A. D., Sebti, S. M., Hamilton, A. D., Muschel, R. J., et al. (1996). The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts. Cancer Res. 56, 1727-1730.
15. + regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2. J. Immunother. 33, 425-434.
16. + NK cells: a functional intermediate stage of NK cell differentiation. J. Immunol. 186, 6753-6761.
17. Bianchi, M. E. (2007). DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 81, 1-5.
18. + regulatory T cells in immune tolerance. Annu. Rev. Immunol. 30, 733-758.
19. + Treg. Eur. J. Immunol. 39, 1323-1333.
20. Blansfield, J. A., Beck, K. E., Tran, K., Yang, J. C., Hughes, M. S., Kammula, U. S., et al. (2005). Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J. Immunother. 28, 593-598.
21. Bluestone, J. A., and Abbas, A. K. (2003). Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3, 253-257.
22. Borges, T. J., Wieten, L., van Herwijnen, M. J., Broere, F., van der Zee, R., Bonorino, C., et al. (2012). The anti-inflammatory mechanisms of Hsp70. Front. Immun. 3:95. doi: 10.3389/fimmu.2012.00095
23. Botzler, C., Issels, R., and Multhoff, G. (1996). Heat-shock protein 72 cell-surface expression on human lung carcinoma cells in association with an increased sensitivity to lysis mediated by adherent natural killer cells. Cancer Immunol. Immunother. 43, 226-230.
24. Botzler, C., Li, G., Issels, R. D., and Multhoff, G. (1998). Definition of extracellular localized epitopes of Hsp70 involved in an NK immune response. Cell Stress Chaperones 3, 6-11.
25. Brahmer, J. R., Drake, C. G., Wollner, I., Powderly, J. D., Picus, J., Sharfman, W. H., et al. (2010). Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 28, 3167-3175.
26. Brahmer, J. R., Tykodi, S. S., Chow, L. Q., Hwu, W. J., Topalian, S. L., Hwu, P., et al. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455-2465.
27. Bronstein, Y., Ng, C. S., Hwu, P., and Hwu, W. J. (2011). Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy. AJR Am. J. Roentgenol. 197, W992-W1000.
28. Bruder, D., Probst-Kepper, M., Westendorf, A. M., Geffers, R., Beissert, S., Loser, K., et al. (2004). Neuropilin-1: a surface marker of regulatory T cells. Eur. J. Immunol. 34, 623-630.
29. Bubenik, J. (2003). Tumour MHC class I downregulation and immunotherapy. Oncol. Rep. 10, 2005-2008.
30. Busse, A., Asemissen, A. M., Nonnenmacher, A., Braun, F., Ochsenreither, S., Stather, D., et al. (2011). Immunomodulatory effects of sorafenib on peripheral immune effector cells in metastatic renal cell carcinoma. Eur. J. Cancer 47, 690-696.
31. Caldenhoven, E., Coffer, P., Yuan, J., Van de Stolpe, A., Horn, F., Kruijer, W., et al. (1994). Stimulation of the human intercellular adhesion molecule-1 promoter by interleukin-6 and interferon-gamma involves binding of distinct factors to a palindromic response element. J. Biol. Chem. 269, 21146-21154.
32. Calderwood, S. K., Khaleque, M. A., Sawyer, D. B., and Ciocca, D. R. (2006). Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem. Sci. 31, 164-172.
33. Calderwood, S. K., Thériault, J. R., and Gong, J. (2005). Message in a bottle: role of the 70-kDa heat shock protein family in anti-tumor immunity. Eur. J. Immunol. 35, 2518-2527.
34. + regulatory T cells. Lab. Invest. 87, 582-590.
35. Carlsten, M., Norell, H., Bryceson, Y. T., Poschke, I., Schedvins, K., Ljunggren, H. G., et al. (2009). Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J. Immunol. 183, 4921-4930.
36. Carretero, M., Cantoni, C., Bellon, T., Bottino, C., Biassoni, R., Rodriguez, A., et al. (1997). The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules. Eur. J. Immunol. 27, 563-567.
37. + T cells with IFN-γ dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination. J. Immunol. 171, 5931-5939.
38. Cerullo, V., Diaconu, I., Kangasniemi, L., Rajecki, M., Escutenaire, S., Koski, A., et al. (2011). Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Mol. Ther. 19, 1737-1746.
39. Chesney, J., Rasku, M., Clem, A., and Miller, D. (2006). Denileukin diftitox depletes T regulatory cells and causes regression of melanoma metastases in humans (abstract). Eur. J. Cancer Suppl. 4, 84.
40. Conroy, H., Galvin, K. C., Higgins, S. C., and Mills, K. H. (2012). Gene silencing of TGF-beta1 enhances antitumor immunity induced with a dendritic cell vaccine by reducing tumor-associated regulatory T cells. Cancer Immunol. Immunother. 61, 425-431.
41. Curiel, T. J. (2007a). Regulatory T-cell development: is Foxp3 the decider? Nat. Med. 13, 250-253.
42. Curiel, T. J. (2007b). Tregs and rethinking cancer immunotherapy. J. Clin. Invest. 117, 1167-1174.
43. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942-949.
44. Dannull, J., Su, Z., Rizzieri, D., Yang, B. K., Coleman, D., Yancey, D., et al. (2005). Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 115, 3623-3633.
45. Desar, I. M., Jacobs, J. H., Hulsbergen-vandeKaa, C. A., Oyen, W. J., Mulders, P. F., van der Graaf, W. T., et al. (2011). Sorafenib reduces the percentage of tumour infiltrating regulatory T cells in renal cell carcinoma patients. Int. J. Cancer 129, 507-512.
46. de Visser, K. E., Eichten, A., and Coussens, L. M. (2006). Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer 6, 24-37.
47. Dewan, M. Z., Takada, M., Terunuma, H., Deng, X., Ahmed, S., Yamamoto, N., et al. (2009). Natural killer activity of peripheral-blood mononuclear cells in breast cancer patients. Biomed. Pharmacother. 63, 703-706.
48. Diaz, R. M., Galivo, F., Kottke, T., Wongthida, P., Qiao, J., Thompson, J., et al. (2007). Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus. Cancer Res. 67, 2840-2848.
49. Divanovic, S., Trompette, A., Atabani, S. F., Madan, R., Golenbock, D. T., Visintin, A., et al. (2005). Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat. Immunol. 6, 571-578.
50. Dons, E. M., Raimondi, G., Cooper, D. K., and Thomson, A. W. (2012). Induced regulatory T cells: mechanisms of conversion and suppressive potential. Hum. Immunol. 73, 328-334.
51. Emens, L. A., Asquith, J. M., Leatherman, J. M., Kobrin, B. J., Petrik, S., Laiko, M., et al. (2009). Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J. Clin. Oncol. 27, 5911-5918.
52. Ercolini, A. M., Ladle, B. H., Manning, E. A., Pfannenstiel, L. W., Armstrong, T. D., Machiels, J. P., et al. (2005). Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response. J. Exp. Med. 201, 1591-1602.
53. + regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res. 63, 6042-6050.
54. Evdonin, A. L., Martynova, M. G., Bystrova, O. A., Guzhova, I. V., Margulis, B. A., and Medvedeva, N. D. (2006). The release of Hsp70 from A431 carcinoma cells is mediated by secretory-like granules. Eur. J. Cell Biol. 85, 443-455.
55. Facciabene, A., Motz, G. T., and Coukos, G. (2012). T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res. 72, 2162-2171.
56. Facciabene, A., Peng, X., Hagemann, I. S., Balint, K., Barchetti, A., Wang, L. P., et al. (2011). Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 475, 226-230.
57. Foss, F. M. (2000). DAB(389)IL-2 (ONTAK): a novel fusion toxin therapy for lymphoma. Clin. Lymphoma 1, 110-116.
58. Freeman, G. J., Wherry, E. J., Ahmed, R., and Sharpe, A. H. (2006). Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J. Exp. Med. 203, 2223-2227.
59. Fugier-Vivier, I., de Bouteiller, O., Guret, C., Fossiez, F., Banchereau, J., Mattei, M. G., et al. (1997). Molecular cloning of human RP105. Eur. J. Immunol. 27, 1824-1827.
60. Fulton, A., Miller, F., Weise, A., and Wei, W. Z. (2006). Prospects of controlling breast cancer metastasis by immune intervention. Breast Dis. 26, 115-127.
61. Garcia-Iglesias, T., Del Toro-Arreola, A., Albarran-Somoza, B., Del Toro-Arreola, S., Sanchez-Hernandez, P. E., Ramirez-Duenas, M. G., et al. (2009). Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer 9:186. doi: 10.1186/1471-2407-9-186
62. Garrido, F., and Algarra, I. (2001). MHC antigens and tumor escape from immune surveillance. Adv. Cancer Res. 83, 117-158.
63. Garrido, F., Cabrera, T., Concha, A., Glew, S., Ruiz-Cabello, F., and Stern, P. L. (1993). Natural history of HLA expression during tumour development. Immunol. Today 14, 491-499.
64. Gavin, M., and Rudensky, A. (2003). Control of immune homeostasis by naturally arising regulatory CD4+ T cells. Curr. Opin. Immunol. 15, 690-696.
65. Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., et al. (2007). Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771-775.
66. Gehrmann, M., Doss, B. T., Wagner, M., Zettlitz, K. A., Kontermann, R. E., Foulds, G., et al. (2011). A novel expression and purification system for the production of enzymatic and biologically active human granzyme B. J. Immunol. Methods 371, 8-17.
67. Gehrmann, M., Liebisch, G., Schmitz, G., Anderson, R., Steinem, C., De Maio, A., et al. (2008a). Tumor-specific Hsp70 plasma membrane localization is enabled by the glycophospholipid Gb3. PLoS ONE 3:e1925. doi: 10.1371/journal.pone.0001925
68. Gehrmann, M., Radons, J., Molls, M., and Multhoff, G. (2008b). The therapeutic implications of clinically applied modifiers of heat shock protein 70 (Hsp70) expression by tumor cells. Cell Stress Chaperones 13, 1-10.
69. Gehrmann, M., Pfister, K., Hutzler, P., Gastpar, R., Margulis, B., and Multhoff, G. (2002). Effects of antineoplastic agents on cytoplasmic and membrane-bound heat shock protein 70 (Hsp70) levels. Biol. Chem. 383, 1715-1725.
70. Gehrmann, M., Schilling, D., Molls, M., and Multhoff, G. (2010). Radiation induced stress proteins. Int. J. Clin. Pharmacol. Ther. 48, 492-493.
71. Gehrmann, M., Stangl, S., Kirschner, A., Foulds, G. A., Sievert, W., Doss, B. T., et al. (2012). Immunotherapeutic targeting of membrane hsp70-expressing tumors using recombinant human granzyme B. PLoS ONE 7:e41341. doi: 10.1371/journal.pone.0041341
72. + regulatory T cells inhibit natural killer cell functions in a transforming growth factor-β-dependent manner. J. Exp. Med. 202, 1075-1085.
73. + regulatory T cell proliferation. J. Exp. Med. 202, 919-929.
74. Golgher, D., Jones, E., Powrie, F., Elliott, T., and Gallimore, A. (2002). Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur. J. Immunol. 32, 3267-3275.
75. + T lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 108, 10656-10661.
76. Graca, L. (2005). New tools to identify regulatory T cells. Eur. J. Immunol. 35, 1678-1680.
77. Grauer, O. M., Nierkens, S., Bennink, E., Toonen, L. W., Boon, L., Wesseling, P., et al. (2007). CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int. J. Cancer 121, 95-105.
78. Gross, C., Hansch, D., Gastpar, R., and Multhoff, G. (2003a). Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol. Chem. 384, 267-279.
79. Gross, C., Schmidt-Wolf, I. G., Nagaraj, S., Gastpar, R., Ellwart, J., Kunz-Schughart, L. A., et al. (2003b). Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells. Cell Stress Chaperones 8, 348-360.
80. Groth, A., Kloss, S., von Strandmann, E. P., Koehl, U., and Koch, J. (2011). Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance. J. Innate Immun. 3, 344-354.
81. Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., de Vries, J. E., et al. (1997). A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742.
82. Gupta, A. K., Cerniglia, G. J., Mick, R., Ahmed, M. S., Bakanauskas, V. J., Muschel, R. J., et al. (2003). Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int. J. Radiat. Oncol. Biol. Phys. 56, 846-853.
83. Gupta, A. K., McKenna, W. G., Weber, C. N., Feldman, M. D., Goldsmith, J. D., Mick, R., et al. (2002). Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin. Cancer Res. 8, 885-892.
84. Guzhova, I., Kislyakova, K., Moskaliova, O., Fridlanskaya, I., Tytell, M., Cheetham, M., et al. (2001). In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res. 914, 66-73.
85. Hallahan, D., Kuchibhotla, J., and Wyble, C. (1996). Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. Cancer Res. 56, 5150-5155.
86. Handschel, J., Prott, F. J., Sunderkotter, C., Metze, D., Meyer, U., and Joos, U. (1999). Irradiation induces increase of adhesion molecules and accumulation of ß2-integrin-expressing cells in humans. Int. J. Radiat. Oncol. Biol. Phys. 45, 475-481.
87. Harrington, K. J., Karapanagiotou, E. M., Roulstone, V., Twigger, K. R., White, C. L., Vidal, L., et al. (2010). Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. Clin. Cancer Res. 16, 3067-3077.
88. Harrington, K. J., Melcher, A., Vassaux, G., Pandha, H. S., and Vile, R. G. (2008). Exploiting synergies between radiation and oncolytic viruses. Curr. Opin. Mol. Ther. 10, 362-370.
89. Henderson, B., Calderwood, S. K., Coates, A. R., Cohen, I., van Eden, W., Lehner, T., et al. (2010). Caught with their PAMS down? The extracellular signalling actions of molecular chaperones are not due to microbial contaminants. Cell Stress Chaperones 15, 123-141.
90. Henderson, B., and Pockley, A. G. (2010). Molecular chaperones and protein folding catalysts as intercellular signaling regulators in immunity and inflammation. J. Leukoc. Biol. 88, 445-462.
91. Hingorani, M., White, C. L., Agrawal, V. K., Vidal, L., Melcher, A., and Harrington, K. J. (2007). Combining radiation and cancer gene therapy: a potential marriage of physical and biological targeting? Curr. Cancer Drug Targets 7, 389-409.
92. Holt, D., Ma, X., Kundu, N., and Fulton, A. (2011). Prostaglandin E2 (PGE2) suppresses natural killer cell function primarily through the PGE2 receptor EP4. Cancer Immunol. Immunother. 60, 1577-1586.
93. + regulatory T cells enhances natural killer T cell-mediated anti-tumour immunity in a murine mammary breast cancer model. Clin. Exp. Immunol. 159, 93-99.
94. Hurwitz, M. D., Kaur, P., Nagaraja, G. M., Bausero, M. A., Manola, J., and Asea, A. (2010). Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer. Radiother. Oncol. 95, 350-358.
95. Iademarco, M. F., McQuillan, J. J., Rosen, G. D., and Dean, D. C. (1992). Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J. Biol. Chem. 267, 16323-16329.
96. dim NK cells in gastric and esophageal cancer: possible mechanisms of NK cell dysfunction. Cancer Immunol. Immunother. 60, 1801-1810.
97. Jacobs, J. F., Idema, A. J., Bol, K. F., Nierkens, S., Grauer, O. M., Wesseling, P., et al. (2009). Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. Neuro Oncol. 11, 394-402.
98. Jacobs, J. F., Nierkens, S., Figdor, C. G., de Vries, I. J., and Adema, G. J. (2012). Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy? Lancet Oncol. 13, e32-e42.
99. Jager, M. J., Hurks, H. M., Levitskaya, J., and Kiessling, R. (2002). HLA expression in uveal melanoma: there is no rule without some exception. Hum. Immunol. 63, 444-451.
100. Jimenez-Perez, M. I., Jave-Suarez, L. F., Ortiz-Lazareno, P. C., Bravo-Cuellar, A., Gonzalez-Ramella, O., Aguilar-Lemarroy, A., et al. (2012). Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications. BMC Immunol. 13:7. doi: 10.1186/1471-2172-13-7
101. Johnsen, A. K., France, J., Nagy, N., Askew, D., Abdul-Karim, F. W., Gerson, S. L., et al. (2001). Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence. Int. J. Cancer 91, 366-372.
102. Jones, E., Dahm-Vicker, M., Simon, A. K., Green, A., Powrie, F., Cerundolo, V., et al. (2002). Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun. 2, 1.
103. + T cells with regulatory properties isolated from peripheral blood. J. Exp. Med. 193, 1285-1294.
104. Karlhofer, F. M., Ribaudo, R. K., and Yokoyama, W. M. (1992). MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells. Nature 358, 66-70.
105. Kärre, K., Ljunggren, H. G., Piontek, G., and Kiessling, R. (1986). Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675-678.
106. Kawai, T., and Akira, S. (2011). Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650.
107. Kiessling, R., Klein, E., and Wigzell, H. (1975). "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur. J. Immunol. 5, 112-117.
108. Kitamura, N., Murata, S., Ueki, T., Mekata, E., Reilly, R. T., Jaffee, E. M., et al. (2009). OX40 costimulation can abrogate Foxp3+ regulatory T cell-mediated suppression of antitumor immunity. Int. J. Cancer 125, 630-638.
109. + regulatory T-cell activity to suppress alloimmune responses. Transplantation 83, 774-782.
110. Klein, O., Ebert, L. M., Nicholaou, T., Browning, J., Russell, S. E., Zuber, M., et al. (2009). Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4. Clin. Cancer Res. 15, 2507-2513.
111. Knutson, K. L., Dang, Y., Lu, H., Lukas, J., Almand, B., Gad, E., et al. (2006). IL-2 immunotoxin therapy modulates tumor-associated regulatory T cells and leads to lasting immune-mediated rejection of breast cancers in neu-transgenic mice. J. Immunol. 177, 84-91.
112. Kozin, S. V., Kamoun, W. S., Huang, Y., Dawson, M. R., Jain, R. K., and Duda, D. G. (2010). Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation. Cancer Res. 70, 5679-5685.
113. Laheru, D., Lutz, E., Burke, J., Biedrzycki, B., Solt, S., Onners, B., et al. (2008). Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin. Cancer Res. 14, 1455-1463.
114. Langers, I., Renoux, V. M., Thiry, M., Delvenne, P., and Jacobs, N. (2012). Natural killer cells: role in local tumor growth and metastasis. Biologics 6, 73-82.
115. Le, D. T., and Jaffee, E. M. (2012). Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: a current perspective. Cancer Res. 72, 3439-3444.
116. + regulatory T cells: evidence for in vivo inhibition of effector cell proliferation. J. Immunol. 172, 6539-6544.
117. Lee, W. C., Zhong, C., Qian, S., Wan, Y., Gauldie, J., Mi, Z., et al. (1998). Phenotype, function, and in vivo migration and survival of allogeneic dendritic cell progenitors genetically engineered to express TGF-ß. Transplantation 66, 1810-1817.
118. Levings, M. K., Sangregorio, R., Galbiati, F., Squadrone, S., de Waal Malefyt, R., and Roncarolo, M. G. (2001a). IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol. 166, 5530-5539.
119. + T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J. Exp. Med. 193, 1295-1302.
120. + regulatory T cell is increased in the patients with ovarian carcinoma. Cancer Invest. 23, 399-403.
121. Lindau, D., Gielen, P., Kroesen, M., Wesseling, P., and Adema, G. J. (2013). The immunosuppressive tumor network: MDSCs, Tregs and NKT cells. Immunology 138, 105-115.
122. + regulatory T cells. Proc. Natl. Acad. Sci. U.S.A. 103, 7048-7053.
123. + T reg cells. J. Exp. Med. 203, 1701-1711.
124. + T regulatory cells: role of tumor-derived TGF-β. J. Immunol. 178, 2883-2892.
125. Liyanage, U. K., Goedegebuure, P. S., Moore, T. T., Viehl, C. T., Moo-Young, T. A., Larson, J. W., et al. (2006). Increased prevalence of regulatory T cells (Treg) is induced by pancreas adenocarcinoma. J. Immunother. 29, 416-424.
126. Liyanage, U. K., Moore, T. T., Joo, H. G., Tanaka, Y., Herrmann, V., Doherty, G., et al. (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.
127. Ljunggren, H. G., and Kärre, K. (1990). In search of the 'missing self': MHC molecules and NK cell recognition. Immunol. Today 11, 237-244.
128. Loke, P., and Allison, J. P. (2003). PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells. Proc. Natl. Acad. Sci. U.S.A. 100, 5336-5341.
129. 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.
130. Machiels, J. P., Reilly, R. T., Emens, L. A., Ercolini, A. M., Lei, R. Y., Weintraub, D., et al. (2001). Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res. 61, 3689-3697.
131. Madjd, Z., Spendlove, I., Pinder, S. E., Ellis, I. O., and Durrant, L. G. (2005). Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. Int. J. Cancer 117, 248-255.
132. Mahnke, K., Bedke, T., and Enk, A. H. (2007a). Regulatory conversation between antigen presenting cells and regulatory T cells enhance immune suppression. Cell. Immunol. 250, 1-13.
133. + human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int. J. Cancer 120, 2723-2733.
134. Mailloux, A. W., and Young, M. R. (2009). NK-dependent increases in CCL22 secretion selectively recruits regulatory T cells to the tumor microenvironment. J. Immunol. 182, 2753-2765.
135. 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.
136. Mambula, S. S., and Calderwood, S. K. (2006a). Heat induced release of Hsp70 from prostate carcinoma cells involves both active secretion and passive release from necrotic cells. Int. J. Hyperthermia 22, 575-585.
137. Mambula, S. S., and Calderwood, S. K. (2006b). Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J. Immunol. 177, 7849-7857.
138. Mamessier, E., Sylvain, A., Bertucci, F., Castellano, R., Finetti, P., Houvenaeghel, G., et al. (2011a). Human breast tumor cells induce self-tolerance mechanisms to avoid NKG2D-mediated and DNAM-mediated NK cell recognition. Cancer Res. 71, 6621-6632.
139. Mamessier, E., Sylvain, A., Thibult, M. L., Houvenaeghel, G., Jacquemier, J., Castellano, R., et al. (2011b). Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J. Clin. Invest. 121, 3609-3622.
140. Manda, K., Glasow, A., Paape, D., and Hildebrandt, G. (2012). Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells. Front. Oncol. 2:102. doi: 10.3389/fonc.2012.00102
141. Mandapathil, M., Szczepanski, M. J., Szajnik, M., Ren, J., Jackson, E. K., Johnson, J. T., et al. (2010). Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J. Biol. Chem. 285, 27571-27580.
142. Marincola, F. M., Jaffee, E. M., Hicklin, D. J., and Ferrone, S. (2000). Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv. Immunol. 74, 181-273.
143. Martinovic, K. M., Konjevic, G., Babovic, N., and Inic, M. (2011). The stage dependent changes in NK cell activity and the expression of activating and inhibitory NK cell receptors in melanoma patients. J. Surg. Res. 171, 637-649.
144. Matsumura, S., and Demaria, S. (2010). Up-regulation of the pro-inflammatory chemokine CXCL16 is a common response of tumor cells to ionizing radiation. Radiat. Res. 173, 418-425.
145. Matsumura, S., Wang, B., Kawashima, N., Braunstein, S., Badura, M., Cameron, T. O., et al. (2008). Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J. Immunol. 181, 3099-3107.
146. + regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease. J. Immunol. 168, 5979-5983.
147. McKenna, W. G., Muschel, R. J., Gupta, A. K., Hahn, S. M., and Bernhard, E. J. (2003). The RAS signal transduction pathway and its role in radiation sensitivity. Oncogene 22, 5866-5875.
148. Mencin, A., Kluwe, J., and Schwabe, R. F. (2009). Toll-like receptors as targets in chronic liver diseases. Gut 58, 704-720.
149. Ménétrier-Caux, C., Curiel, T., Faget, J., Manuel, M., Caux, C., and Zou, W. (2012). Targeting regulatory T cells. Target Oncol. 7, 15-28.
150. Menon, A. G., Morreau, H., Tollenaar, R. A., Alphenaar, E., Van Puijenbroek, M., Putter, H., et al. (2002). Down-regulation of HLA-A expression correlates with a better prognosis in colorectal cancer patients. Lab. Invest. 82, 1725-1733.
151. Miyake, K., Yamashita, Y., Ogata, M., Sudo, T., and Kimoto, M. (1995). RP105, a novel B cell surface molecule implicated in B cell activation, is a member of the leucine-rich repeat protein family. J. Immunol. 154, 3333-3340.
152. Molenkamp, B. G., van Leeuwen, P. A., Meijer, S., Sluijter, B. J., Wijnands, P. G., Baars, A., et al. (2007). Intradermal CpG-B activates both plasmacytoid and myeloid dendritic cells in the sentinel lymph node of melanoma patients. Clin. Cancer Res. 13, 2961-2969.
153. + regulatory T-cells in hematologic diseases. Korean J. Lab. Med. 31, 231-237.
154. Moretta, A., Vitale, M., Bottino, C., Orengo, A. M., Morelli, L., Augugliaro, R., et al. (1993). P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J. Exp. Med. 178, 597-604.
155. Mori, N., and Prager, D. (1996). Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins. Blood 87, 3410-3417.
156. Motoyoshi, Y., Kaminoda, K., Saitoh, O., Hamasaki, K., Nakao, K., Ishii, N., et al. (2006). Different mechanisms for anti-tumor effects of low-and high-dose cyclophosphamide. Oncol. Rep. 16, 141-146.
157. Mougiakakos, D., Johansson, C. C., Trocme, E., All-Ericsson, C., Economou, M. A., Larsson, O., et al. (2010). Intratumoral forkhead box P3-positive regulatory T cells predict poor survival in cyclooxygenase-2-positive uveal melanoma. Cancer 116, 2224-2233.
158. Multhoff, G. (2007). Heat shock protein 70 (Hsp70): membrane location, export and immunological relevance. Methods 43, 229-237.
159. Multhoff, G. (2009). Activation of natural killer cells by heat shock protein 70. 2002. Int. J. Hyperthermia 25, 169-175.
160. Multhoff, G., Botzler, C., Jennen, L., Schmidt, J., Ellwart, J., and Issels, R. (1997). Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J. Immunol. 158, 4341-4350.
161. Multhoff, G., Botzler, C., Wiesnet, M., Muller, E., Meier, T., Wilmanns, W., et al. (1995). A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int. J. Cancer 61, 272-279.
162. Multhoff, G., and Hightower, L. E. (1996). Cell surface expression of heat shock proteins and the immune response. Cell Stress Chaperones 1, 167-176.
163. Multhoff, G., Pfister, K., Gehrmann, M., Hantschel, M., Gross, C., Hafner, M., et al. (2001). A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity. Cell Stress Chaperones 6, 337-344.
164. Multhoff, G., and Radons, J. (2012). Radiation, inflammation, and immune responses in cancer. Front. Oncol. 2:58. doi: 10.3389/fonc.2012.00058
165. Nagler, A., Lanier, L. L., Cwirla, S., and Phillips, J. H. (1989). Comparative studies of human FcRIII-positive and negative natural killer cells. J. Immunol. 143, 3183-3191.
166. Nelson, B. H. (2004). IL-2, regulatory T cells, and tolerance. J. Immunol. 172, 3983-3988.
167. Oberg, H. H., Juricke, M., Kabelitz, D., and Wesch, D. (2011). Regulation of T cell activation by TLR ligands. Eur. J. Cell Biol. 90, 582-592.
168. Onizuka, S., Tawara, I., Shimizu, J., Sakaguchi, S., Fujita, T., and Nakayama, E. (1999). Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 59, 3128-3133.
169. Ozao-Choy, J., Ma, G., Kao, J., Wang, G. X., Meseck, M., Sung, M., et al. (2009). The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res. 69, 2514-2522.
170. + regulatory T cell function. Science 309, 1380-1384.
171. Piconese, S., Valzasina, B., and Colombo, M. P. (2008). OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J. Exp. Med. 205, 825-839.
172. Pockley, A. G. (2003). Heat shock proteins and their role as regulators of the immune response. Lancet 362, 469-476.
173. Pockley, A. G., Bulmer, J., Hanks, B. M., and Wright, B. H. (1999). Identification of human heat shock protein 60 (Hsp60) and anti-Hsp60 antibodies in the peripheral circulation of normal individuals. Cell Stress Chaperones 4, 29-35.
174. Pockley, A. G., Shepherd, J., and Corton, J. (1998). Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol. Invest. 27, 367-377.
175. Pockley, A. G., Wu, R., Lemne, C., Kiessling, R., de Faire, U., and Frostegård, J. (2000). Circulating heat shock protein 60 is associated with early cardiovascular disease. Hypertension 36, 303-307.
176. Prestwich, R. J., Harrington, K. J., Pandha, H. S., Vile, R. G., Melcher, A. A., and Errington, F. (2008). Oncolytic viruses: a novel form of immunotherapy. Expert Rev. Anticancer Ther. 8, 1581-1588.
177. Raimondi, G., Turner, M. S., Thomson, A. W., and Morel, P. A. (2007). Naturally occurring regulatory T cells: recent insights in health and disease. Crit. Rev. Immunol. 27, 61-95.
178. Ralph, C., Elkord, E., Burt, D. J., O'Dwyer, J. F., Austin, E. B., Stern, P. L., et al. (2010). Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma. Clin. Cancer Res. 16, 1662-1672.
179. Ramnath, N., Tan, D., Li, Q., Hylander, B. L., Bogner, P., Ryes, L., et al. (2006). Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival? Cancer Immunol. Immunother. 55, 891-899.
180. Rea, I. M., McNerlan, S., and Pockley, A. G. (2001). Serum heat shock protein and anti-heat shock protein antibody levels in aging. Exp. Gerontol. 36, 341-352.
181. Rech, A. J., and Vonderheide, R. H. (2009). Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann. N.Y. Acad. Sci. 1174, 99-106.
182. Reits, E. A., Hodge, J. W., Herberts, C. A., Groothuis, T. A., Chakraborty, M., Wansley, E. K., et al. (2006). Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med. 203, 1259-1271.
183. Restifo, N. P. (1996). The new vaccines: building viruses that elicit antitumor immunity. Curr. Opin. Immunol. 8, 658-663.
184. Rödel, F., Frey, B., Manda, K., Hildebrandt, G., Hehlgans, S., Keilholz, L., et al. (2012). Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation. Front. Oncol. 2:120. doi: 10.3389/fonc.2012.00120
185. Roncarolo, M. G., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., and Levings, M. K. (2006). Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 212, 28-50.
186. Rubner, Y., Wunderlich, R., Ruhle, P. F., Kulzer, L., Werthmoller, N., Frey, B., et al. (2012). How does ionizing irradiation contribute to the induction of anti-tumor immunity? Front. Oncol. 2:75. doi: 10.3389/fonc.2012.00075
187. Rudge, G., Barrett, S. P., Scott, B., and van Driel, I. R. (2007). Infiltration of a mesothelioma by IFN-γ-producing cells and tumor rejection after depletion of regulatory T cells. J. Immunol. 178, 4089-4096.
188. Russell, J. S., Lang, F. F., Huet, T., Janicot, M., Chada, S., Wilson, D. R., et al. (1999). Radiosensitization of human tumor cell lines induced by the adenovirus-mediated expression of an anti-Ras single-chain antibody fragment. Cancer Res. 59, 5239-5244.
189. Saito, H., Osaki, T., and Ikeguchi, M. (2012). Decreased NKG2D expression on NK cells correlates with impaired NK cell function in patients with gastric cancer. Gastric Cancer 15, 27-33.
190. + regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22, 531-562.
191. Sakaguchi, S. (2011). Regulatory T cells: history and perspective. Methods Mol. Biol. 707, 3-17.
192. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164.
193. Savage, P. A., Malchow, S., and Leventhal, D. S. (2013). Basic principles of tumor-associated regulatory T cell biology. Trends Immunol. 34, 33-40.
194. Schilling, D., Gehrmann, M., Steinem, C., De Maio, A., Pockley, A. G., Abend, M., et al. (2009). Binding of heat shock protein 70 to extracellular phosphatidylserine promotes killing of normoxic and hypoxic tumor cells. FASEB J. 23, 2467-2477.
195. Schindler, U., and Baichwal, V. R. (1994). Three NF-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression. Mol. Cell. Biol. 14, 5820-5831.
196. Schmetterer, K. G., Neunkirchner, A., and Pickl, W. F. (2012). Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J. 26, 2253-2276.
197. Schmid, T. E., and Multhoff, G. (2012). Non-targeted effects of photon and particle irradiation and the interaction with the immune system. Front. Oncol. 2:80. doi: 10.3389/fonc.2012.00080
198. Schmidtner, J., Distel, L. V., Ott, O. J., Nkenke, E., Sprung, C. N., Fietkau, R., et al. (2009). Hyperthermia and irradiation of head and neck squamous cancer cells causes migratory profile changes of tumour infiltrating lymphocytes. Int. J. Hyperthermia 25, 347-354.
199. + regulatory T cells in human head and neck carcinoma during radio-chemotherapy. Eur. J. Med. Res. 16, 57-62.
200. Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., et al. (2006). Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203, 1693-1700.
201. Shakhov, A. N., Collart, M. A., Vassalli, P., Nedospasov, S. A., and Jongeneel, C. V. (1990). Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J. Exp. Med. 171, 35-47.
202. Shan, Y. X., Jin, S. Z., Liu, X. D., Liu, Y., and Liu, S. Z. (2007). Ionizing radiation stimulates secretion of pro-inflammatory cytokines: dose-response relationship, mechanisms and implications. Radiat. Environ. Biophys 46, 21-29.
203. + suppressor T cells: more questions than answers. Nat. Rev. Immunol. 2, 389-400.
204. Shevach, E. M. (2011). Biological functions of regulatory T cells. Adv. Immunol. 112, 137-176.
205. Shiao, S. L., and Coussens, L. M. (2010). The tumor-immune microenvironment and response to radiation therapy. J. Mammary Gland Biol. Neoplasia 15, 411-421.
206. + T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 163, 5211-5218.
207. Shin, B. K., Wang, H., Yim, A. M., Le Naour, F., Brichory, F., Jang, J. H., et al. (2003). Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J. Biol. Chem. 278, 7607-7616.
208. Song, B., Song, W. G., Li, Z. J., Xu, Z. F., Wang, X. W., Wang, C. X., et al. (2011). Effect of HMGB1 silencing on cell proliferation, invasion and apoptosis of MGC-803 gastric cancer cells. Cell Biochem. Funct. 30, 11-17.
209. Stangl, S., Gehrmann, M., Dressel, R., Alves, F., Dullin, C., Themelis, G., et al. (2010). In vivo imaging of CT26 mouse tumors by using cmHsp70.1 monoclonal antibody. J. Cell. Mol. Med. 15, 874-887.
210. Stangl, S., Gehrmann, M., Riegger, J., Kuhs, K., Riederer, I., Sievert, W., et al. (2011). Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc. Natl. Acad. Sci. U.S.A. 108, 733-738.
211. + T cells resulting in a failure to lyse tumor cells. Blood 93, 1634-1642.
212. Steinbrink, K., Wolfl, M., Jonuleit, H., Knop, J., and Enk, A. H. (1997). Induction of tolerance by IL-10-treated dendritic cells. J. Immunol. 159, 4772-4780.
213. + T-cell-dependent immune defense of B16 melanoma. Cancer Res. 61, 8643-8646.
214. Stobo, J. D., Rosenthal, A. S., and Paul, W. E. (1973). Functional heterogeneity of murine lymphoid cells. V. Lymphocytes lacking detectable surface theta or immunoglobulin determinants. J. Exp. Med. 138, 71-88.
215. Stocki, P., Wang, X. N., and Dickinson, A. M. (2012). Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells. J. Biol. Chem. 287, 12387-12394.
216. + T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin. Cancer Res. 13, 4345-4354.
217. + T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J. Immunol. 160, 1212-1218.
218. + regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J. Exp. Med. 194, 823-832.
219. Suzuki, Y., Mimura, K., Yoshimoto, Y., Watanabe, M., Ohkubo, Y., Izawa, S., et al. (2012). Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res. 72, 3967-3976.
220. Thompson, R. H., Dong, H., Lohse, C. M., Leibovich, B. C., Blute, M. L., Cheville, J. C., et al. (2007). PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin. Cancer Res. 13, 1757-1761.
221. Topalian, S. L., Drake, C. G., and Pardoll, D. M. (2012a). Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr. Opin. Immunol. 24, 207-212.
222. Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012b). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454.
223. Twigger, K., Vidal, L., White, C. L., De Bono, J. S., Bhide, S., Coffey, M., et al. (2008). Enhanced in vitro and in vivo cytotoxicity of combined reovirus and radiotherapy. Clin. Cancer Res. 14, 912-923.
224. van Maren, W. W., Jacobs, J. F., de Vries, I. J., Nierkens, S., and Adema, G. J. (2008). Toll-like receptor signalling on Tregs: to suppress or not to suppress? Immunology 124, 445-452.
225. + regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice. Ann. Surg. Oncol. 13, 1252-1258.
226. Vigouroux, S., Yvon, E., Biagi, E., and Brenner, M. K. (2004). Antigen-induced regulatory T cells. Blood 104, 26-33.
227. Vivier, E., Nunes, J. A., and Vely, F. (2004). Natural killer cell signaling pathways. Science 306, 1517-1519.
228. Vivier, E., Raulet, D. H., Moretta, A., Caligiuri, M. A., Zitvogel, L., Lanier, L. L., et al. (2011). Innate or adaptive immunity? The example of natural killer cells. Science 331, 44-49.
229. Vivier, E., Tomasello, E., Baratin, M., Walzer, T., and Ugolini, S. (2008). Functions of natural killer cells. Nat. Immunol. 9, 503-510.
230. Waldmann, H., Graca, L., Cobbold, S., Adams, E., Tone, M., and Tone, Y. (2004). Regulatory T cells and organ transplantation. Semin. Immunol. 16, 119-126.
231. Wan, Y. Y., and Flavell, R. A. (2007). Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445, 766-770.
232. Wang, M. H., Grossmann, M. E., and Young, C. Y. (2004). Forced expression of heat-shock protein 70 increases the secretion of Hsp70 and provides protection against tumour growth. Br. J. Cancer 90, 926-931.
233. Hi regulatory T cells. Int. Immunol. 21, 1065-1077.
234. Whiteside, T. L. (2012). What are regulatory T cells (Treg) regulating in cancer and why? Semin. Cancer Biol. 22, 327-334.
235. Wickremasinghe, M. I., Thomas, L. H., O'Kane, C. M., Uddin, J., and Friedland, J. S. (2004). Transcriptional mechanisms regulating alveolar epithelial cell-specific CCL5 secretion in pulmonary tuberculosis. J. Biol. Chem. 279, 27199-27210.
236. Wolchok, J. D., Weber, J. S., Hamid, O., Lebbe, C., Maio, M., Schadendorf, D., et al. (2010). Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials. Cancer Immun. 10, 9.
237. Wolf, A. M., Wolf, D., Steurer, M., Gastl, G., Gunsilius, E., and Grubeck-Loebenstein, B. (2003). Increase of regulatory T cells in the peripheral blood of cancer patients. Clin. Cancer Res. 9, 606-612.
238. Wood, K. J., and Sakaguchi, S. (2003). Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 3, 199-210.
239. high regulatory T cell numbers and FOXP3 mRNA expression in patients with advanced esophageal cancer before and after chemotherapy. Cell Biochem. Biophys. 61, 389-392.
240. + regulatory T cells from human peripheral blood. J. Immunol. 166, 7282-7289.
241. + regulatory T cells through the production of TGF-beta1. World J. Gastroenterol. 17, 2019-2027.
242. Zaidi, S. H., Huddart, R. A., and Harrington, K. J. (2009). Novel targeted radiosensitisers in cancer treatment. Curr. Drug Discov. Technol. 6, 103-134.
243. Zhang, Y., Luo, F., Cai, Y., Liu, N., Wang, L., Xu, D., et al. (2011). TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells. J. Immunol. 186, 1963-1969.
244. Zheng, P., Sarma, S., Guo, Y., and Liu, Y. (1999). Two mechanisms for tumor evasion of preexisting cytotoxic T-cell responses: lessons from recurrent tumors. Cancer Res. 59, 3461-3467.
245. Zhou, G., and Levitsky, H. I. (2007). Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J. Immunol. 178, 2155-2162.
246. Zou, W. (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer 5, 263-274.