Various ways to improve whole cancer cell vaccines

Expert Review of Vaccines

Volumn 13, Issue 6, 2014, Pages 721-735

  Cicchelero, Laetitia ^a   De Rooster, Hilde ^a   Sanders, Niek N ^a  

^a GHENT UNIVERSITY   (Belgium)

Author keywords

adjuvants; immune memory; immunogenic cell death; whole cancer cell vaccines

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALRETICULIN; CANCER VACCINE; DNA; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; HIGH MOBILITY GROUP B1 PROTEIN; IMMUNOLOGICAL ADJUVANT; INTERLEUKIN 12; RNA; UNCLASSIFIED DRUG; VACCINE; WHOLE CANCER CELL VACCINE;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN PRESENTATION; CANCER CELL LINE; CANCER IMMUNIZATION; CANCER RECURRENCE; CANCER STEM CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEATH; CELL KILLING; CELLULAR IMMUNITY; DENDRITIC CELL; ENDOPLASMIC RETICULUM STRESS; GRANULOCYTE; HUMAN; HUMORAL IMMUNITY; IMMUNOLOGICAL MEMORY; LYMPHOCYTE DIFFERENTIATION; MACROPHAGE; MEMORY T LYMPHOCYTE; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; VACCINE PRODUCTION; IMMUNOLOGY; IMMUNOTHERAPY; ISOLATION AND PURIFICATION; NEOPLASMS; PROCEDURES;

ADJUVANTS, IMMUNOLOGIC; CANCER VACCINES; HUMANS; IMMUNOTHERAPY; NEOPLASMS;

EID: 84901056524     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.2014.911093     Document Type: Review

References (150)

1. Brown MP, Burdett N. Targeted therapies, aspects of pharmaceutical and oncological management. Cancer Forum 2013;37(1): 70-80
2. Hirschowitz EA, Yannelli JR. Immunotherapy for lung cancer. Proc Am Thorac Soc 2009;6(2):224-32
3. Serhal K, Baillou C, Ghinea N, et al. Characteristics of hybrid cells obtained by dendritic cell/tumour cell fusion in a T-47D breast cancer cell line model indicate their potential as anti-tumour vaccines. Int J Oncol 2007;31(6):1357-65
4. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004;10(9): 909-15
5. Lasaro MO, Ertl HC. Targeting inhibitory pathways in cancer immunotherapy. Curr Opin Immunol 2010;22(3):385-90
6. Gilbert AE, Karagiannis P, Dodev T, et al. Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies. PLoS ONE 2011;6(4):e19330
7. DiFronzo LA, Gupta RK, Essner R, et al. Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J Clin Oncol 2002;20(15):3242-8
8. Aly HA. Cancer therapy and vaccination. J Immunol Methods 2012;382(1-2):1-23
9. Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993;90(8):3539-43
10. Kalos M. Tumor antigen-specific T cells and cancer immunotherapy: current issues and future prospects. Vaccine 2003;21(7-8): 781-6
11. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012; 12(4):237-51
12. Nierkens S, Janssen EM. Harnessing dendritic cells for tumor antigen presentation. Cancers (Basel) 2011;3(2): 2195-213
13. Casares N, Pequignot MO, Tesniere A, et al. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 2005;202(12):1691-701
14. Gamrekelashvili J, Kruger C, von WR, et al. Necrotic tumor cell death in vivo impairs tumor-specific immune responses. J Immunol 2007;178(3):1573-80
15. de Gruijl TD, van den Eertwegh AJ, Pinedo HM, Scheper RJ. Whole-cell cancer vaccination: from autologous to allogeneic tumor-and dendritic cell-based vaccines. Cancer Immunol Immunother 2008;57(10): 1569-77
16. Boog CJ. Principles of vaccination and possible development strategies for rational design. Immunol Lett 2009;122(2):104-7
17. Lesterhuis WJ, Haanen JB, Punt CJ. Cancer immunotherapy-revisited. Nat Rev Drug Discov 2011;10(8):591-600
18. Wang RF. The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity. Trends Immunol 2001;22(5):269-76
19. Palucka K, Ueno H, Banchereau J. Recent developments in cancer vaccines. J Immunol 2011;186(3):1325-31
20. Chang EY, Chen CH, Ji H, et al. Antigen-specific cancer immunotherapy using a GM-CSF secreting allogeneic tumor cell-based vaccine. Int J Cancer 2000;86(5): 725-30
21. Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J Clin Oncol 2003;21(12):2415-32
22. Sauter B, Albert ML, Francisco L, et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 2000;191(3): 423-34
23. Ronchetti A, Rovere P, Iezzi G, et al. Immunogenicity of apoptotic cells in vivo: role of antigen load, antigen-presenting cells, and cytokines. J Immunol 1999;163(1): 130-6
24. Chiang CL, Benencia F, Coukos G. Whole tumor antigen vaccines. Semin Immunol 2010;22(3):132-43
25. Gilboa E. DC-based cancer vaccines. J Clin Invest 2007;117(5):1195-203
26. Bagarazzi ML, Yan J, Morrow MP, et al. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med 2012;4(155):155ra138
27. Chiang CL, Kandalaft LE, Coukos G. Adjuvants for enhancing the immunogenicity of whole tumor cell vaccines. Int Rev Immunol 2011;30(2-3): 150-82
28. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 2011; 480(7378):480-9
29. Andersen BM, Ohlfest JR. Increasing the efficacy of tumor cell vaccines by enhancing cross priming. Cancer Lett 2012;325(2): 155-64
30. Klebanoff CA, Acquavella N, Yu Z, Restifo NP. Therapeutic cancer vaccines: are we there yet? Immunol Rev 2011;239(1):27-44
31. Burchill MA, Tamburini BA, Pennock ND, et al. T cell vaccinology: exploring the known unknowns. Vaccine 2013;31(2): 297-305
32. Ning N, Pan Q, Zheng F, et al. Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res 2012; 72(7):1853-64
33. Li B, Simmons A, Du T, et al. Allogeneic GM-CSF-secreting tumor cell immunotherapies generate potent anti-tumor responses comparable to autologous tumor cell immunotherapies. Clin Immunol 2009;133(2)):184-97
34. Zhou J, Weng D, Zhou F, et al. Patient-derived renal cell carcinoma cells fused with allogeneic dendritic cells elicit anti-tumor activity: in vitro results and clinical responses. Cancer Immunol Immunother 2009;58(10):1587-97
35. Krysko DV, Garg AD, Kaczmarek A, et al. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012; 12(12):860-75
36. Dillman RO, Beutel LD, De LC, Nayak SK Short-term tumor cell lines from breast cancer for use as autologous tumor cell vaccines in the treatment of breast cancer. Cancer Biother Radiopharm 2001; 16(3):205-11
37. Teitz-Tennenbaum S, Wicha MS, Chang AE, Li Q. Targeting cancer stem cells via dendritic-cell vaccination. Oncoimmunology 2012;1(8):1401-3
38. Pellegatta S, Finocchiaro G. Dendritic cell vaccines for cancer stem cells. Methods Mol Biol 2009;568:233-47
39. Finn OJ. Cancer vaccines: between the idea and the reality. Nat Rev Immunol 2003; 3(8):630-41
40. Toes RE, Blom RJ, van d V, et al. Protective antitumor immunity induced by immunization with completely allogeneic tumor cells. Cancer Res 1996;56(16):3782-7
41. Yasuda T, Kamigaki T, Kawasaki K, et al. Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma. Cancer Immunol Immunother 2007;56(7):1025-36
42. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013;31:51-72
43. Kepp O, Galluzzi L, Martins I, et al. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 2011; 30(1):61-9
44. Apetoh L, Obeid M, Tesniere A, et al. Immunogenic chemotherapy: discovery of a critical protein through proteomic analyses of tumor cells. Cancer Genomics Proteomics 2007;4(2):65-70
45. Galluzzi L, Maiuri MC, Vitale I, et al. Cell death modalities: classification and pathophysiological implications. Cell Death Differ 2007;14(7):1237-43
46. Kepp O, Tesniere A, Schlemmer F, et al. Immunogenic cell death modalities and their impact on cancer treatment. Apoptosis 2009;14(4):364-75
47. Korsnes MS. Yessotoxin as a tool to study induction of multiple cell death pathways. Toxins (Basel) 2012;4(7):568-79
48. Gollnick SO, Vaughan L, Henderson BW. Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res 2002;62(6):1604-8
49. Korbelik M, Sun J. Photodynamic therapy-generated vaccine for cancer therapy. Cancer Immunol Immunother 2006;55(8):900-9
50. Garg AD, Krysko DV, Verfaillie T, et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J 2012;31(5):1062-79
51. Fry TJ, Shand JL, Milliron M, et al. Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches. Cancer Immunol Immunother 2009;58(8):1257-64
52. Kim TB, Park HK, Chang JH, et al. The establishment of dendritic cell-tumor fusion vaccines for hormone refractory prostate cancer cell. Korean J Urol 2010;51(2): 139-44
53. Bird RC, Deinnocentes P, Lenz S, et al. An allogeneic hybrid-cell fusion vaccine against canine mammary cancer. Vet Immunol Immunopathol 2008; 123(3-4):289-304
54. Gottesman A, Milazzo J, Lazebnik Y. V-fusion: a convenient, nontoxic method for cell fusion. Biotechniques 2010;49(4): 747-50
55. Usaj M, Kanduser M. The systematic study of the electroporation and electrofusion of B16-F1 and CHO cells in isotonic and hypotonic buffer. J Membr Biol 2012; 245(9):583-90
56. Iinuma H, Okinaga K, Fukushima R, et al. Superior protective and therapeutic effects of IL-12 and IL-18 gene-transduced dendritic neuroblastoma fusion cells on liver metastasis of murine neuroblastoma. J Immunol 2006;176(6):3461-9
57. Radomska HS, Eckhardt LA. Mammalian cell fusion in an electroporation device. J Immunol Methods 1995;188(2): 209-17
58. Gottfried E, Krieg R, Eichelberg C, et al. Characterization of cells prepared by dendritic cell-tumor cell fusion. Cancer Immun 2002;2:15
59. Torabi-Rahvar M, Bozorgmehr M, Jeddi-Tehrani M, Zarnani AH. Potentiation strategies of dendritic cell-based antitumor vaccines: combinational therapy takes the front seat. Drug Discov Today 2011; 16(15-16):733-40
60. Gong J, Nikrui N, Chen D, et al. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 2000;165(3):1705-11
61. Marten A, Renoth S, Heinicke T, et al. Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma. Hum Gene Ther 2003;14(5):483-94
62. Heath WR, Belz GT, Behrens GM, et al. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 2004;199: 9-26
63. Nierkens S, Tel J, Janssen E, Adema GJ. Antigen cross-presentation by dendritic cell subsets: one general or all sergeants? Trends Immunol 2013;34(8):361-70
64. Ali OA, Emerich D, Dranoff G, Mooney DJ. In situ regulation of DC subsets and T cells mediates tumor regression in mice. Sci Transl Med 2009; 1(8):8ra19
65. Kotera Y, Shimizu K, Mule JJ. Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res 2001; 61(22):8105-9
66. Itano AA, Jenkins MK. Antigen presentation to naive CD4 T cells in the lymph node. Nat Immunol 2003;4(8): 733-9
67. Engell-Noerregaard L, Hansen TH, Andersen MH, et al. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immunother 2009;58(1):1-14
68. Castiello L, Sabatino M, Jin P, et al. Monocyte-derived DC maturation strategies and related pathways: a transcriptional view. Cancer Immunol Immunother 2011;60(4): 457-66
69. Huang LY, Sousa Re, Itoh Y, et al. IL-12 induction by a TH1-inducing adjuvant in vivo: dendritic cell subsets and regulation by IL-10. J Immunol 2001; 167(3):1423-30
70. Balwit JM, Hwu P, Urba WJ, Marincola FM. The iSBTc/SITC primer on tumor immunology and biological therapy of cancer: a summary of the 2010 program. J Transl Med 2011;9:18
71. Hailemichael Y, Dai Z, Jaffarzad N, et al. Persistent antigen at vaccination sites induces tumor-specific CD8(+) T cell sequestration, dysfunction and deletion. Nat Med 2013;19(4):465-72
72. Song J, Salek-Ardakani S, Rogers PR, et al. The costimulation-regulated duration of PKB activation controls T cell longevity. Nat Immunol 2004;5(2):150-8
73. Capece D, Verzella D, Fischietti M, et al. Targeting costimulatory molecules to improve antitumor immunity. J Biomed Biotechnol 2012;2012:926321
74. Copier J, Dalgleish A. Overview of tumor cell-based vaccines. Int Rev Immunol 2006; 25(5-6):297-319
75. Gong J, Koido S, Calderwood SK. Cell fusion: from hybridoma to dendritic cell-based vaccine. Expert Rev Vaccines 2008;7(7):1055-68
76. Nanni P, Nicoletti G, De GC, et al. Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice. J Exp Med 2001;194(9): 1195-205
77. Koido S, Tanaka Y, Chen D, et al. The kinetics of in vivo priming of CD4 and CD8 T cells by dendritic/tumor fusion cells in MUC1-transgenic mice. J Immunol 2002; 168(5):2111-17
78. Lindner M, Schirrmacher V. Tumour cell-dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocols. Eur J Clin Invest 2002;32(3):207-17
79. Tamai H, Watanabe S, Zheng R, et al. Effective treatment of spontaneous metastases derived from a poorly immunogenic murine mammary carcinoma by combined dendritic-tumor hybrid vaccination and adoptive transfer of sensitized T cells. Clin Immunol 2008; 127(1):66-77
80. Stannard KA, Collins PM, Ito K, et al. Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. Cancer Lett 2010;299(2):95-110
81. Ahlert T, Sauerbrei W, Bastert G, et al. Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer. J Clin Oncol 1997;15(4):1354-66
82. Dols A, Smith JW, Meijer SL, et al. Vaccination of women with metastatic breast cancer, using a costimulatory gene (CD80)-modified, HLA-A2-matched, allogeneic, breast cancer cell line: clinical and immunological results. Hum Gene Ther 2003;14(11):1117-23
83. Avigan D, Vasir B, Gong J, et al. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res 2004;10(14):4699-708
84. Homma S, Sagawa Y, Ito M, et al. Cancer immunotherapy using dendritic/tumour-fusion vaccine induces elevation of serum anti-nuclear antibody with better clinical responses. Clin Exp Immunol 2006;144(1): 41-7
85. Wang J, Saffold S, Cao X, et al. Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 1998;161(10):5516-24
86. van Elsas A, Hurwitz AA, Allison JP. 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 1999;190(3). 355-66
87. Li J, Holmes LM, Franek KJ, et al. Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity. Cancer Immunol Immunother 2001;50(9):456-62
88. Siders WM, Vergilis KL, Johnson C, et al. Induction of specific antitumor immunity in the mouse with the electrofusion product of tumor cells and dendritic cells. Mol Ther 2003;7(4):498-505
89. Prell RA, Gearin L, Simmons A, et al. The anti-tumor efficacy of a GM-CSF-secreting tumor cell vaccine is not inhibited by docetaxel administration. Cancer Immunol Immunother 2006;55(10):1285-93
90. Krause SW, Neumann C, Soruri A, et al. The treatment of patients with disseminated malignant melanoma by vaccination with autologous cell hybrids of tumor cells and dendritic cells. J Immunother 2002;25(5): 421-8
91. Barbuto JA, Ensina LF, Neves AR, et al. Dendritic cell-tumor cell hybrid vaccination for metastatic cancer. Cancer Immunol Immunother 2004;53(12):1111-18
92. Luiten RM, Kueter EW, Mooi W, et al. Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients. J Clin Oncol 2005;23(35):8978-91
93. Hurn BA, Chantler SM. Production of reagent antibodies. Methods Enzymol 1980; 70(A):104-42
94. Hendriksen C, Hau J. Production of polyclonal and monoclonal antibodies In: Hau J, Van Hoosier GL, editors, Handbook of laboratory animal science. CRC Press, LLC, Boca Raton, FL, USA; 2003. p. 391-411.
95. Morse MA, Coleman RE, Akabani G, et al. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res 1999;59(1): 56-8
96. Widner LA, Teates CD. Distribution of gold Au 198 after intraperitoneal injection in animals. South Med J 1975;68(6): 687-93
97. Fong L, Brockstedt D, Benike C, et al. Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 2001;166(6):4254-9
98. Kjaergaard J, Shimizu K, Shu S. Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine. Cell Immunol 2003;225(2):65-74
99. Draube A, Klein-Gonzalez N, Mattheus S, et al. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS One 2011;6(4):e18801
100. Bedrosian I, Mick R, Xu S, et al. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol 2003;21(20): 3826-35
101. de Vries IJ, Lesterhuis WJ, Barentsz JO, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 2005;23(11):1407-13
102. Korbelik M, Stott B, Sun J. Photodynamic therapy-generated vaccines: relevance of tumour cell death expression. Br J Cancer 2007;97(10):1381-7
103. Munn DH, Mellor AL. The tumor-draining lymph node as an immune-privileged site. Immunol Rev 2006;213:146-58
104. Ohlfest JR, Andersen BM, Litterman AJ, et al. Vaccine injection site matters: qualitative and quantitative defects in CD8 T cells primed as a function of proximity to the tumor in a murine glioma model. J Immunol 2013;190(2):613-20
105. Wick DA, Martin SD, Nelson BH, Webb JR. Profound CD8+ T cell immunity elicited by sequential daily immunization with exogenous antigen plus the TLR3 agonist poly(I:C). Vaccine 2011; 29(5):984-93
106. Heikenwalder M, Polymenidou M, Junt T, et al. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat Med 2004;10(2):187-92
107. Avigan D, Rosenblatt J, Kufe D. Dendritic/tumor fusion cells as cancer vaccines. Semin Oncol 2012;39(3):287-95
108. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12(4):252-64
109. Tesniere A, Panaretakis T, Kepp O, et al. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 2008; 15(1):3-12
110. Vacchelli E, Galluzzi L, Rousseau V, et al. Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer. Oncoimmunology 2012;1(3):271-8
111. Apetoh L, Mignot G, Panaretakis T, et al. Immunogenicity of anthracyclines: moving towards more personalized medicine. Trends Mol Med 2008;14(4):141-51
112. Blankenstein T, Coulie PG, Gilboa E, Jaffee EM. The determinants of tumour immunogenicity. Nat Rev Cancer 2012; 12(4):307-13
113. Schlom J, Gulley JL, Arlen PM. Paradigm shifts in cancer vaccine therapy. Exp Biol Med (Maywood) 2008;233(5):522-34
114. Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 2007;13(1):54-61
115. Zitvogel L, Kroemer G. Introduction: the immune response against dying cells. Curr Opin Immunol 2008;20(5):501-3
116. Kuylenstierna C, Bjorkstrom NK, Andersson SK, et al. NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d. EurJ Immunol 2011;41(7):1913-23
117. Zafirova B, Wensveen FM, Gulin M, Polic B. Regulation of immune cell function and differentiation by the NKG2D receptor. Cell Mol Life Sci 2011;68(21):3519-29
118. la Sala A, Ferrari D, Corinti S, et al. Extracellular ATP induces a distorted maturation of dendritic cells and inhibits their capacity to initiate Th1 responses. J Immunol 2001;166(3):1611-17
119. Frey B, Schildkopf P, Rodel F, et al. AnnexinA5 renders dead tumor cells immunogenic-implications for multimodal cancer therapies. J Immunotoxicol 2009; 6(4):209-16
120. Aymeric L, Apetoh L, Ghiringhelli F, et al. Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 2010;70(3):855-8
121. Spisek R, Charalambous A, Mazumder A, et al. Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications. Blood 2007; 109(11):4839-45
122. Ding ZC, Zhou G. Cytotoxic chemotherapy and CD4+ effector T cells: an emerging alliance for durable antitumor effects. Clin Dev Immunol 2012;2012:890178
123. Weiss EM, Meister S, Janko C, et al. High hydrostatic pressure treatment generates inactivated mammalian tumor cells with immunogeneic features. J Immunotoxicol 2010;7(3):194-204
124. Ito A, Shinkai M, Honda H, et al. Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia. Cancer Immunol Immunother 2001;50(10): 515-22
125. Shi H, Cao T, Connolly JE, et al. Hyperthermia enhances CTL cross-priming. J Immunol 2006;176(4):2134-41
126. Fucikova J, Kralikova P, Fialova A, et al. Human tumor cells killed by anthracyclines induce a tumor-specific immune response. Cancer Res 2011;71(14):4821-33
127. Menard C, Martin F, Apetoh L, et al. Cancer chemotherapy: not only a direct cytotoxic effect, but also an adjuvant for antitumor immunity. Cancer Immunol Immunother 2008;57(11): 1579-87
128. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity 2010;33(4):492-503
129. Steinhagen F, Kinjo T, Bode C, Klinman DM. TLR-based immune adjuvants. Vaccine 2011;29(17):3341-55
130. Link C, Gavioli R, Ebensen T, et al. The Toll-like receptor ligand MALP-2 stimulates dendritic cell maturation and modulates proteasome composition and activity. Eur J Immunol 2004;34(3):899-907
131. Krug A, Towarowski A, Britsch S, et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. EurJ Immunol 2001;31(10): 3026-37
132. Gladue RP, Paradis T, Cole SH, et al. The CD40 agonist antibody CP-870, 893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice. Cancer Immunol Immunother 2011;60(7):1009-17
133. Postow M, Callahan MK, Wolchok JD. Beyond cancer vaccines: a reason for future optimism with immunomodulatory therapy. Cancer J 2011;17(5):372-8
134. Melero I, Hirschhorn-Cymerman D, Morales-Kastresana A, et al. Agonist antibodies to TNFR molecules that costimulate T and NK cells. Clin Cancer Res 2013;19(5):1044-53
135. Wang S. The promise of cancer therapeutics targeting the TNF-related apoptosis-inducing ligand and TRAIL receptor pathway. Oncogene 2008;27(48): 6207-15
136. Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 2005;78(5):1043-51
137. Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol 2010;28(10): 1069-78
138. Pratap J, Akech J, Wixted JJ, et al. The histone deacetylase inhibitor, vorinostat, reduces tumor growth at the metastatic bone site and associated osteolysis, but promotes normal bone loss. Mol Cancer Ther 2010;9(12):3210-20
139. Yong X, Xiao YF, Luo G, et al. Strategies for enhancing vaccine-induced CTL antitumor immune responses. J Biomed Biotechnol 2012;2012: 605045
140. Velasco-Velazquez M, Jiao X, De La Fuente M, et al. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res 2012;72(15):3839-50
141. Schlom J. Therapeutic cancer vaccines: current status and moving forward. J Natl Cancer Inst 2012;104(8):599-613
142. Ko HJ, Lee JM, Kim YJ, et al. Immunosuppressive myeloid-derived suppressor cells can be converted into immunogenic APCs with the help of activated NKT cells: an alternative cell-based antitumor vaccine. J Immunol 2009;182(4): 1818-28
143. Liu Y, Zeng B, Zhang Z, et al. B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer. Clin Immunol 2008;129(3):471-81
144. Vincent J, Mignot G, Chalmin F, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 2010; 70(8):3052-61
145. Morris SM Jr. Recent advances in arginine metabolism: roles and regulation of the arginases. Br J Pharmacol 2009;157(6): 922-30
146. Munder M. Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol 2009;158(3):638-51
147. Vivier E, Ugolini S, Blaise D, et al. Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 2012;12(4):239-52
148. Gyrd-Hansen M, Meier P. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer 2010;10(8):561-74
149. Kameshima H, Tsuruma T, Kutomi G, et al. Immunotherapeutic benefit of alpha-interferon (IFNalpha) in survivin2B-derived peptide vaccination for advanced pancreatic cancer patients. Cancer Sci 2013;104(1):124-9
150. Hedvat M, Huszar D, Herrmann A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 2009;16(6): 487-97