Combination of cancer immunotherapy with clinically available drugs that can block immunosuppressive cells

Immunological Investigations

Volumn 43, Issue 6, 2014, Pages 517-534

  Kim, So Jung ^a   Ha, Ga Hee ^a   Kim, Sun Hee ^a   Kang, Chi Dug ^a  

^a Pusan National University School of Medicine   (South Korea)

Author keywords

Anticancer drugs; Cancer immunotherapy; Immunosuppressive microenvironments

Indexed keywords

ANTINEOPLASTIC AGENT; B7 ANTIGEN; BEVACIZUMAB; BISPHOSPHONIC ACID DERIVATIVE; CANCER VACCINE; CD86 ANTIGEN; CYCLOOXYGENASE 2 INHIBITOR; CYCLOPHOSPHAMIDE; FLUDARABINE; FLUOROURACIL; GEMCITABINE; IMMUNOMODULATING AGENT; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 4; INTERLEUKIN 7; IPILIMUMAB; L SELECTIN; PACLITAXEL; PROSTAGLANDIN E2; PROSTAGLANDIN G; RANTES; RETINOIC ACID; SILDENAFIL; SUNITINIB; THYMIC STROMAL LYMPHOPOIETIN; TUMOR NECROSIS FACTOR ALPHA; IMMUNOSUPPRESSIVE AGENT; TUMOR ANTIGEN;

ADAPTIVE IMMUNITY; CANCER CHEMOTHERAPY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER SURGERY; CELL MATURATION; CELLULAR IMMUNITY; CHRONIC LYMPHATIC LEUKEMIA; CYTOKINE PRODUCTION; DENDRITIC CELL; DRUG TREATMENT FAILURE; GRANULOCYTE; HUMAN; IMMUNE RESPONSE; IMMUNITY; IMMUNOLOGICAL TOLERANCE; IMMUNOSUPPRESSIVE TREATMENT; MACROPHAGE; MOLECULARLY TARGETED THERAPY; NATURAL KILLER CELL; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; TUMOR REGRESSION; ADOPTIVE IMMUNOTHERAPY; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; DRUG THERAPY; IMMUNOLOGY; MULTIMODALITY CANCER THERAPY; NEOPLASMS; TUMOR ESCAPE;

ANIMALS; ANTIGENS, NEOPLASM; CANCER VACCINES; COMBINED MODALITY THERAPY; DRUG THERAPY; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY, ADOPTIVE; NEOPLASMS; TUMOR ESCAPE; TUMOR MICROENVIRONMENT;

EID: 84903997593     PISSN: 08820139     EISSN: 15324311     Source Type: Journal    
DOI: 10.3109/08820139.2013.857352     Document Type: Review

References (99)

1. Almand B, Clark JI, Nikitina E, et al. (2001 Increased production of immature myeloid cells in cancer patients: A mechanism of immunosuppression in cancer. J Immunol, 166, 678-89. (Pubitemid 32038493)
2. Apetoh L, Locher C, Ghiringhelli F, et al. (2011 Harnessing dendritic cells in cancer. Semin Immunol, 23, 42-9.
3. Armeanu S, Bitzer M, Lauer UM, et al. (2005 Natural killer cell-mediated lysis of hepatoma cells via specific induction of NKG2D ligands by the histone deacetylase inhibitor sodium valproate. Cancer Res, 65, 6321-9. (Pubitemid 40994418)
4. Bauer C, Dauer M, Saraj S, et al. (2011 Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: Results of a pilot study. Cancer Immunol Immunother, 60, 1097-107.
5. Berd D, Maguire Jr HC, Mastrangelo MJ. (1986 Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide. Cancer Res, 46, 2572-7. (Pubitemid 16120733)
6. Berd D, Mastrangelo MJ. (1988 Effect of low dose cyclophosphamide on the immune system of cancer patients: Depletion of CD4\+, 2H4\+ suppressor-inducer T-cells. Cancer Res, 48, 1671-5. (Pubitemid 18091225)
7. Beyer M, Kochanek M, Darabi K, et al. (2005 Reduced frequencies and suppressive function of CD4\+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood, 106, 2018-25. (Pubitemid 41291715)
8. Capuano G, Rigamonti N, Grioni M, et al. (2009 Modulators of arginine metabolism support cancer immunosurveillance. BMC Immunol, 10, 1471-2174.
9. Cerullo V, Diaconu I, Kangasniemi L, et al. (2011 Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Mol Ther, 19, 1737-46.
10. Chakraborty M, Abrams SI, Coleman CN, et al. (2004 External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccinemediated T-cell killing. Cancer Res, 64, 4328-37. (Pubitemid 38802440)
11. Correale P, Cusi MG, Tsang KY, et al. (2005 Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients. J Clin Oncol, 23, 8950-8. (Pubitemid 46211480)
12. Dietz AB, Souan L, Knutson GJ, et al. (2004 Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood, 104, 1094-9. (Pubitemid 39038030)
13. Djeu J, Wei S. (2012 Chemoimmunomodulation of MDSCs as a novel strategy for cancer therapy. Oncoimmunology, 1, 121-2.
14. Dumitriu IE, Dunbar DR, Howie SE, et al. (2009 Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4\+CD25\+Foxp3\+ regulatory T cells. J Immunol, 182, 2795-807.
15. Duperron C, Castonguay A. (1997 Chemopreventive efficacies of aspirin and sulindac against lung tumorigenesis in A/J mice. Carcinogenesis, 18, 1001-6. (Pubitemid 28132346)
16. Ellebaek E, Engell-Noerregaard L, Iversen TZ, et al. (2012 Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide: Results from a phase II trial. Cancer Immunol Immunother, 61, 1791-804.
17. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. (2010 The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol, 10, 554-67.
18. Fricke I, Mirza N, Dupont J, et al. (2007 Vascular endothelial growth factor-trap overcomes defects in dendritic cell differentiation but does not improve antigenspecific immune responses. Clin Cancer Res, 13, 4840-8. (Pubitemid 47298146)
19. Fridlender ZG, Albelda SM. (2012 Tumor-associated neutrophils: Friend or foe? Carcinogenesis, 33, 949-55.
20. Fridlender ZG, Sun J, Kim S, et al. (2009 Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN. Cancer Cell, 16, 183-94.
21. Fridman WH, Pages F, Sautes-Fridman C, Galon J. (2012 The immune contexture in human tumours: Impact on clinical outcome. Nat Rev Cancer, 12, 298-306.
22. Frumento G, Rotondo R, Tonetti M, et al. (2002 Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med, 196, 459-68.
23. Ge Y, Domschke C, Stoiber N, et al. (2012 Metronomic cyclophosphamide treatment in metastasized breast cancer patients: Immunological effects and clinical outcome. Cancer Immunol Immunother, 61, 353-62.
24. Ghiringhelli F, Larmonier N, Schmitt E, et al. (2004 CD4\+CD25\+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol, 34, 336-44. (Pubitemid 39255944)
25. Ghiringhelli F, Menard C, Puig PE, et al. (2007 Metronomic cyclophosphamide regimen selectively depletes CD4\+CD25\+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother, 56, 641-8. (Pubitemid 46348738)
26. Glaser M. (1979 Regulation of specific cell-mediated cytotoxic response against SV40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice. J Exp Med, 149, 774-9. (Pubitemid 9137688)
27. Hegde U, Chhabra A, Chattopadhyay S, et al. (2008 Presence of low dose of fludarabine in cultures blocks regulatory T cell expansion and maintains tumorspecific cytotoxic T lymphocyte activity generated with peripheral blood lymphocytes. Pathobiology, 75, 200-8.
28. Higano CS, Schellhammer PF, Small EJ, et al. (2009 Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer, 115, 3670-9.
29. Hodi FS, O'Day SJ, McDermott DF, et al. (2010 Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med, 363, 711-23.
30. Hoechst B, Ormandy LA, Ballmaier M, et al. (2008 A new population of myeloidderived suppressor cells in hepatocellular carcinoma patients induces CD4(\+)CD25(\+)Foxp3(\+) T cells. Gastroenterology, 135, 234-43. (Pubitemid 351899008)
31. Ishizaki H, Manuel ER, Song GY, et al. (2011 Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model. Cancer Immunol Immunother, 60, 99-109.
32. Khong HT, Restifo NP. (2002 Natural selection of tumor variants in the generation of "tumor escape" phenotypes. Nat Immunol, 3, 999-1005. (Pubitemid 35363649)
33. Kim JY, Son YO, Park SW, et al. (2006 Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation. Exp Mol Med, 38, 474-84.
34. Ko HJ, Kim YJ, Kim YS, et al. (2007 A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor model. Cancer Res, 67, 7477-86.
35. Ko JS, Zea AH, Rini BI, et al. (2009 Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res, 15, 2148-57.
36. Kodumudi KN, Woan K, Gilvary DL, et al. (2010 A novel chemoimmunomodulating property of docetaxel: Suppression of myeloid-derived suppressor cells in tumor bearers. Clin Cancer Res, 16, 4583-94.
37. Kohlmeyer J, Cron M, Landsberg J, et al. (2009 Complete regression of advanced primary and metastatic mouse melanomas following combination chemoimmunotherapy. Cancer Res, 69, 6265-74.
38. Kusmartsev S, Cheng F, Yu B, et al. (2003 All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res, 63, 4441-9. (Pubitemid 36951016)
39. Kusmartsev S, Eruslanov E, Kubler H, et al. (2008 Oxidative stress regulates expression of VEGFR1 in myeloid cells: Link to tumor-induced immune suppression in renal cell carcinoma. J Immunol, 181, 346-53.
40. Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. (2004 Antigen-specific inhibition of CD8\+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol, 172, 989-99. (Pubitemid 38113758)
41. Kusmartsev S, Su Z, Heiser A, et al. (2008 Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res, 14, 8270-8.
42. Kwon HK, Lee CG, So JS, et al. (2010 Generation of regulatory dendritic cells and CD4\+Foxp3\+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci USA, 107, 2159-64.
43. Le DT, Jaffee EM. (2012 Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: A current perspective. Cancer Res, 72, 3439-44.
44. Leahy KM, Ornberg RL, Wang Y, et al. (2002 Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res, 62, 625-31. (Pubitemid 34126930)
45. Levin G, Kariv N, Khomiak E, Raz A. (2000 Indomethacin inhibits the accumulation of tumor cells in mouse lungs and subsequent growth of lung metastases. Chemotherapy, 46, 429-37.
46. Liu Q, Zhang C, Sun A, et al. (2009 Tumor-educated CD11bhighIalow regulatory dendritic cells suppress T cell response through arginase I. J Immunol, 182, 6207-16.
47. Liu WM, Fowler DW, Smith P, Dalgleish AG. (2010 Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses. Br J Cancer, 102, 115-23.
48. Lutsiak ME, Semnani RT, De Pascalis R, et al. (2005 Inhibition of CD4(\+)25\+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood, 105, 2862-8. (Pubitemid 40446280)
49. MacLean GD, Miles DW, Rubens RD, et al. (1996 Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J Immunother Emphasis Tumor Immunol, 19, 309-16. (Pubitemid 26313521)
50. Madan RA, Mohebtash M, Arlen PM, et al. (2012 Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: A phase 1 dose-escalation trial. Lancet Oncol, 13, 501-8.
51. Malmberg KJ. (2004 Effective immunotherapy against cancer: A question of overcoming immune suppression and immune escape? Cancer Immunol Immunother, 53, 879-92.
52. Medina-Echeverz J, Fioravanti J, Zabala M, et al. (2011 Successful colon cancer eradication after chemoimmunotherapy is associated with profound phenotypic change of intratumoral myeloid cells. J Immunol, 186, 807-15.
53. Melani C, Sangaletti S, Barazzetta FM, et al. (2007 Amino-biphosphonate- mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloidderived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res, 67, 11438-46. (Pubitemid 350248572)
54. Meyer C, Sevko A, Ramacher M, et al. (2011 Chronic inflammation promotes myeloidderived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model. Proc Natl Acad Sci USA, 108, 17111-6.
55. Mirza N, Fishman M, Fricke I, et al. (2006 All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res, 66, 9299-307. (Pubitemid 44521152)
56. Miyazawa M, Ohsawa R, Tsunoda T, et al. (2010 Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci, 101, 433-9.
57. Mkrtichyan M, Najjar YG, Raulfs EC, et al. (2011 Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms. Eur J Immunol, 41, 2977-86.
58. Mocellin S, Nitti D. (2008 Therapeutics targeting tumor immune escape: Towards the development of new generation anticancer vaccines. Med Res Rev, 28, 413-44. (Pubitemid 351590541)
59. Mosser DM, Edwards JP. (2008 Exploring the full spectrum of macrophage activation. Nat Rev Immunol, 8, 958-69.
60. Muller AJ, Scherle PA. (2006 Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors. Nat Rev Cancer, 6, 613-25. (Pubitemid 44140859)
61. Munn DH, Sharma MD, Lee JR, et al. (2002 Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science, 297, 1867-70. (Pubitemid 35024345)
62. Nefedova Y, Fishman M, Sherman S, et al. (2007 Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells. Cancer Res, 67, 11021-8. (Pubitemid 350145932)
63. Nishioka Y, Aono Y, Sone S. (2011 Role of tyrosine kinase inhibitors in tumor immunology. Immunotherapy, 3, 107-16.
64. Norian LA, Rodriguez PC, O'Mara LA, et al. (2009 Tumor-infiltrating regulatory dendritic cells inhibit CD8\+ T cell function via L-arginine metabolism. Cancer Res, 69, 3086-94.
65. Ostrand-Rosenberg S. (2010 Myeloid-derived suppressor cells: More mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother, 59, 1593-600.
66. Ozao-Choy J, Ma G, Kao J, 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, 2514-22.
67. Park YS, Bae JH, Son CH, et al. (2011 Cyclophosphamide potentiates the antitumor effect of immunization with injection of immature dendritic cells into irradiated tumor. Immunol Invest, 40, 383-99.
68. Polak L, Turk JL. (1974 Reversal of immunological tolerance by cyclophosphamide through inhibition of suppressor cell activity. Nature, 249, 654-6.
69. Reits EA, Hodge JW, Herberts CA, et al. (2006 Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med, 203, 1259-71. (Pubitemid 43736595)
70. Rettig L, Seidenberg S, Parvanova I, et al. (2011 Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells. Int J Cancer, 129, 832-8.
71. Rochman Y, Spolski R, Leonard WJ. (2009 New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol, 9, 480-90.
72. Rodriguez PC, Ernstoff MS, Hernandez C, et al. (2009 Arginase I-producing myeloidderived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res, 69, 1553-60.
73. Rosenberg SA, Yang JC, Restifo NP. (2004 Cancer immunotherapy: Moving beyond current vaccines. Nat Med, 10, 909-15. (Pubitemid 39273730)
74. Rotondo R, Barisione G, Mastracci L, et al. (2009 IL-8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer. Int J Cancer, 125, 887-93.
75. Serafini P, Meckel K, Kelso M, et al. (2006 Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med, 203, 2691-702. (Pubitemid 44833345)
76. Serafini P, Mgebroff S, Noonan K, Borrello I. (2008 Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res, 68, 5439-49.
77. Shurin MR, Naiditch H, Zhong H, Shurin GV. (2011 Regulatory dendritic cells: New targets for cancer immunotherapy. Cancer Biol Ther, 11, 988-92.
78. Son CH, Shin DY, Kim SD, et al. (2012 Improvement of antitumor effect of intratumoral injection of immature dendritic cells into irradiated tumor by cyclophosphamide in mouse colon cancer model. J Immunother, 35, 607-14.
79. Song X, Guo W, Cui J, et al. (2011 A tritherapy combination of a fusion protein vaccine with immune-modulating doses of sequential chemotherapies in an optimized regimen completely eradicates large tumors in mice. Int J Cancer, 128, 1129-38.
80. Stewart TJ, Greeneltch KM, Lutsiak ME, Abrams SI. (2007 Immunological responses can have both pro-and antitumour effects: Implications for immunotherapy. Expert Rev Mol Med, 9, 1-20. (Pubitemid 46242913)
81. Strimpakos AS, Syrigos KN, Saif MW. (2012 Novel agents in early phase clinical studies on refractory pancreatic cancer. JOP, 13, 166-8.
82. Suzuki E, Kapoor V, Jassar AS, et al. (2005 Gemcitabine selectively eliminates splenic Gr-1\+/CD11b\+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res, 11, 6713-21. (Pubitemid 41339014)
83. Talmadge JE, Hood KC, Zobel LC, et al. (2007 Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. Int Immunopharmacol, 7, 140-51. (Pubitemid 46043318)
84. Todaro M, Orlando V, Cicero G, et al. (2013 Chemotherapy sensitizes colon cancer initiating cells to Vgamma9Vdelta2 T cell-mediated cytotoxicity. PLoS One, 8, e65145.
85. Tsubouchi Y, Mukai S, Kawahito Y, et al. (2000 Meloxicam inhibits the growth of non-small cell lung cancer. Anticancer Res, 20, 2867-72.
86. van den Eertwegh AJ, Versluis J, van den Berg HP, et al. (2012 Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: A phase 1 dose-escalation trial. Lancet Oncol, 13, 509-17.
87. van Elsas A, Hurwitz AA, Allison JP. (1999 Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med, 190, 355-66. (Pubitemid 29374833)
88. Vignali DA, Collison LW, Workman CJ. (2008 How regulatory T cells work. Nat Rev Immunol, 8, 523-32.
89. Vincent J, Mignot G, Chalmin F, et al. (2010 5-Fluorouracil selectively kills tumorassociated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res, 70, 3052-61.
90. Wada J, Suzuki H, Fuchino R, et al. (2009 The contribution of vascular endothelial growth factor to the induction of regulatory T-cells in malignant effusions. Anticancer Res, 29, 881-8.
91. Walter S, Weinschenk T, Stenzl A, et al. (2012 Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med, 18, 1254-61.
92. Xin H, Zhang C, Herrmann A, et al. (2009 Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res, 69, 2506-13.
93. Yaguchi T, Sumimoto H, Kudo-Saito C, et al. (2011 The mechanisms of cancer immunoescape and development of overcoming strategies. Int J Hematol, 93, 294-300.
94. Yanagimoto H, Shiomi H, Satoi S, et al. (2010 A phase II study of personalized peptide vaccination combined with gemcitabine for non-resectable pancreatic cancer patients. Oncol Rep, 24, 795-801.
95. Yu H, Kortylewski M, Pardoll D. (2007 Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nat Rev Immunol, 7, 41-51. (Pubitemid 46020826)
96. Zea AH, Rodriguez PC, Atkins MB, et al. (2005 Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion. Cancer Res, 65, 3044-8. (Pubitemid 40524582)
97. Zhu Y, Liu N, Xiong SD, et al. (2011 CD4\+Foxp3\+ regulatory T-cell impairment by paclitaxel is independent of toll-like receptor 4. Scand J Immunol, 73, 301-8.
98. Zitvogel L, Apetoh L, Ghiringhelli F, et al. (2008 The anticancer immune response: Indispensable for therapeutic success? J Clin Invest, 118, 1991-2001. (Pubitemid 351872317)
99. Zou W. (2005 Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer, 5, 263-74. (Pubitemid 40488632)