Immunogenic versus tolerogenic phagocytosis during anticancer therapy: Mechanisms and clinical translation

Cell Death and Differentiation

Volumn 23, Issue 6, 2016, Pages 938-951

  Garg, A D ^a   Romano, E ^a   Rufo, N ^a   Agostinis, P ^a  

^a LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; ANTINEOPLASTIC AGENT; BIOLOGICAL MARKER; CALRETICULIN; CD47 ANTIGEN; DEATH DOMAIN RECEPTOR 1ALPHA; DEATH RECEPTOR; HEAT SHOCK PROTEIN 90; PHOSPHATIDYLSERINE; UNCLASSIFIED DRUG; ALARMIN; IMMUNOGLOBULIN RECEPTOR;

ANTIGEN PRESENTING CELL; APOPTOSIS; ARTICLE; CANCER CELL; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; HUMAN; IMMUNOGENICITY; NEOPLASM; PHAGOCYTE; PHAGOCYTOSIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PREDICTION; PRIORITY JOURNAL; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ALARMINS; APOPTOSIS; CD47 ANTIGEN; HSP90 HEAT-SHOCK PROTEINS; HUMANS; IMMUNOTHERAPY; NEOPLASMS; PHAGOCYTOSIS; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION;

EID: 84958787375     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/cdd.2016.5     Document Type: Article

References (158)

1. Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM., et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol 2015; 6: 588
2. Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D., et al. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 2015 22: 58-73
3. Garg AD, Martin S, Golab J, Agostinis P. Danger signalling during cancer cell death: origins, plasticity and regulation. Cell Death Differ 2014; 21: 26-38
4. Griffith TS, Ferguson TA. Cell death in the maintenance and abrogation of tolerance: the five Ws of dying cells. Immunity 2011; 35: 456-466
5. Ravichandran KS. Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity 2011; 35: 445-455
6. Gregory CD, Brown SB. Apoptosis: eating sensibly. Nat Cell Biol 2005; 7: 1161-1163
7. Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P. Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta 2010; 1805: 53-71
8. Petrovski G, Zahuczky G, Katona K, Vereb G, Martinet W, Nemes Z., et al. Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes. Cell Death Differ 2007; 14: 1117-1128
9. Green DR, Ferguson T, Zitvogel L, Kroemer G. Immunogenic and tolerogenic cell death. Nat Rev Immunol 2009; 9: 353-363
10. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF., et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009; 461: 282-286
11. Yang D, De la Rosa G, Tewary P, Oppenheim JJ. Alarmins link neutrophils and dendritic cells. Trends Immunol 2009; 30: 531-537
12. Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell 2010; 140: 798-804
13. Chao MP, Jaiswal S, Weissman-Tsukamoto R, Alizadeh AA, Gentles AJ, Volkmer J., et al. Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med 2010; 2: 63ra94
14. Poon IK, Hulett MD, Parish CR. Molecular mechanisms of late apoptotic/necrotic cell clearance. Cell Death Differ 2010; 17: 381-397
15. Birge RB, Ucker DS. Innate apoptotic immunity: the calming touch of death. Cell Death Differ 2008; 15: 1096-1102
16. Krysko DV, Vandenabeele P. Clearance of dead cells: mechanisms, immune responses and implication in the development of diseases. Apoptosis 2010; 15: 995-997
17. Coulie PG, Van den Eynde BJ, Van Der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 2014; 14: 135-146
18. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science 2015; 348: 69-74
19. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31: 51-72
20. Garg AD, Dudek AM, Agostinis P. Cancer immunogenicity, danger signals, and DAMPs: what, when, and how?. Biofactors 2013; 39: 355-367
21. Venereau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life. Front Immunol 2015; 6: 422
22. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H., et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigenpresenting cells. Immunity 2013; 38: 729-741
23. Aderem A. Phagocytosis and the inflammatory response. J Infect Dis 2003; 187(Suppl 2): S340-S345
24. Maderna P, Godson C. Phagocytosis of apoptotic cells and the resolution of inflammation. Biochim Biophys Acta 2003; 1639: 141-151
25. Dudek AM, Martin S, Garg AD, Agostinis P. Immature, semi-mature, and fully mature dendritic cells: toward a DC-cancer cells interface that augments anticancer immunity. Front Immunol 2013; 4: 438
26. Garg AD, Dudek-Peric AM, Agostinis P. Melphalan, antimelanoma immunity, and inflammation-response. Cancer Res 2015; 75: 5400-5401
27. Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 2015; 16: 907-917
28. Krysko DV, Vandenabeele P. From regulation of dying cell engulfment to development of anti-cancer therapy. Cell Death Differ 2008; 15: 29-38
29. Segawa K, Nagata S. An apoptotic 'eat me' signal: phosphatidylserine exposure. Trends Cell Biol 2015; 25: 639-650
30. Derer A, Deloch L, Rubner Y, Fietkau R, Frey B, Gaipl US. Radio-immunotherapy-induced immunogenic cancer cells as basis for induction of systemic anti-tumor immune responses - pre-clinical evidence and ongoing clinical applications. Front Immunol 2015; 6: 505
31. Newton K, Dugger DL, Wickliffe KE, Kapoor N, De Almagro MC, Vucic D., et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 2014; 343: 1357-1360
32. Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB. Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ 2008; 15: 171-182
33. Fulda S. Caspase-8 in cancer biology and therapy. Cancer Lett 2009; 281: 128-133
34. Krysko DV, D'Herde K, Vandenabeele P. Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 2006; 11: 1709-1726
35. Kearney CJ, Cullen SP, Tynan GA, Henry CM, Clancy D, Lavelle EC., et al. Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production. Cell Death Differ 2015; 22: 1313-1327
36. Garg AD, Dudek AM, Ferreira GB, Verfaillie T, Vandenabeele P, Krysko DV., et al. ROSinduced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy 2013; 9: 1292-1307
37. Verfaillie T, Van Vliet A, Garg AD, Dewaele M, Rubio N, Gupta S., et al. Pro-Apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim. Biochem Biophys Res Commun 2013; 438: 500-506
38. Garg AD, Dudek AM, Agostinis P. Calreticulin surface exposure is abrogated in cells lacking, chaperone-mediated autophagy-essential gene, LAMP2A. Cell Death Dis 2013; 4: e826
39. Petrovski G, Ayna G, Majai G, Hodrea J, Benko S, Madi A., et al. Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1beta release in human macrophages. Autophagy 2011; 7: 321-330
40. Brouckaert G, Kalai M, Krysko DV, Saelens X, Vercammen D, Ndlovu MN., et al. Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. Mol Biol Cell 2004; 15: 1089-1100
41. Geijtenbeek TB. Actin' as a death signal. Immunity 2012; 36: 557-559
42. Lauber K, Keppeler H, Munoz LE, Koppe U, Schroder K, Yamaguchi H., et al. Milk fat globule- EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids. Cell Death Differ 2013; 20: 1230-1240
43. Bondanza A, Zimmermann VS, Rovere-Querini P, Turnay J, Dumitriu IE, Stach CM., et al. Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo. J Exp Med 2004; 200: 1157-1165
44. Jinushi M, Nakazaki Y, Dougan M, Carrasco DR, Mihm M, Dranoff G. MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- And antiinflammatory activities of GM-CSF. J Clin Invest 2007; 117: 1902-1913
45. Balasubramanian K, Maeda A, Lee JS, Mohammadyani D, Dar HH, Jiang JF., et al. Dichotomous roles for externalized cardiolipin in extracellular signaling: Promotion of phagocytosis and attenuation of innate immunity. Sci Signal 2015; 8: ra95
46. Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 2014; 14: 166-180
47. Vacchelli E, Ma Y, Baracco EE, Sistigu A, Enot DP, Pietrocola F., et al. Chemotherapyinduced antitumor immunity requires formyl peptide receptor 1. Science 2015; 350: 972-978
48. Yang Y, Li XJ, Chen Z, Zhu XX, Wang J, Zhang LB., et al. Wogonin induced calreticulin/ annexin A1 exposure dictates the immunogenicity of cancer cells in a PERK/AKT dependent manner. PLoS One 2012; 7: e50811
49. Yoon KW, Byun S, Kwon E, Hwang SY, Chu K, Hiraki M., et al. Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science 2015; 349: 1261669
50. Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE., et al. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through transactivation of LRP on the phagocyte. Cell 2005; 123: 321-334
51. Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buque A, Senovilla L, Baracco EE., et al. Classification of current anticancer immunotherapies. Oncotarget 2014; 5: 12472-12508
52. Garg AD, Elsen S, Krysko DV, Vandenabeele P, De Witte P, Agostinis P. Resistance to anticancer vaccination effect is controlled by a cancer cell-Autonomous phenotype that disrupts immunogenic phagocytic removal. Oncotarget 2015; 6: 26841-26860
53. Garg AD, Dudek-Peric AM, Romano E, Agostinis P. Immunogenic cell death. Int J Dev Biol 2015; 59: 131-140
54. Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012; 12: 860-875
55. Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P., et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 2014; 3: e955691
56. Dudek-Peric AM, Ferreira GB, Muchowicz A, Wouters J, Prada N, Martin S., et al. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-Associated calreticulin. Cancer Res 2015; 75: 1603-1614
57. Martin S, Dudek-Peric AM, Maes H, Garg AD, Gabrysiak M, Demirsoy S., et al. Concurrent MEK and autophagy inhibition is required to restore cell death associated danger-signalling in Vemurafenib-resistant melanoma cells. Biochem Pharmacol 2015; 93: 290-304
58. Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP., et al. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 2012; 19: 1880-1891
59. Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T., et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J 2012; 31: 1062-1079
60. Panaretakis T, Kepp O, Brockmeier U, Tesniere A, Bjorklund AC, Chapman DC., et al. Mechanisms of pre-Apoptotic calreticulin exposure in immunogenic cell death. EMBO J 2009; 28: 578-590
61. Garg AD, Krysko DV, Vandenabeele P, Agostinis P. Hypericin-based photodynamic therapy induces surface exposure of damage-Associated molecular patterns like HSP70 and calreticulin. Cancer Immunol Immunother 2012; 61: 215-221
62. Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res 2010; 16: 3100-3104
63. Gopal U, Bohonowych JE, Lema-Tome C, Liu A, Garrett-Mayer E, Wang B., et al. A novel extracellular Hsp90 mediated co-receptor function for LRP1 regulates EphA2 dependent glioblastoma cell invasion. PLoS One 2011; 6: e17649
64. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL., et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 2007; 13: 54-61
65. Pawaria S, Binder RJ. CD91-dependent programming of T-helper cell responses following heat shock protein immunization. Nat Commun 2011; 2: 521
66. Zappasodi R, Pupa SM, Ghedini GC, Bongarzone I, Magni M, Cabras AD., et al. Improved clinical outcome in indolent B-cell lymphoma patients vaccinated with autologous tumor cells experiencing immunogenic death. Cancer Res 2010; 70: 9062-9072
67. Fucikova J, Kralikova P, Fialova A, Brtnicky T, Rob L, Bartunkova J., et al. Human tumor cells killed by anthracyclines induce a tumor-specific immune response. Cancer Res 2011; 71: 4821-4833
68. Oldenborg PA. CD47: a cell surface glycoprotein which regulates multiple functions of hematopoietic cells in health and disease. ISRN Hematol 2013; 2013: 614619
69. Olsson M, Bruhns P, Frazier WA, Ravetch JV, Oldenborg PA. Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia. Blood 2005; 105: 3577-3582
70. Okazawa H, Motegi S, Ohyama N, Ohnishi H, Tomizawa T, Kaneko Y., et al. Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. J Immunol 2005; 174: 2004-2011
71. Nilsson A, Oldenborg PA. CD47 promotes both phosphatidylserine-independent and phosphatidylserine-dependent phagocytosis of apoptotic murine thymocytes by nonactivated macrophages. Biochem Biophys Res Commun 2009; 387: 58-63
72. Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr., et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 2009; 138: 286-299
73. Zhao XW, Van Beek EM, Schornagel K, Van Der Maaden H, Van Houdt M, Otten M.A., et al. CD47-signal regulatory protein-Alpha (SIRPalpha) interactions form a barrier for antibodymediated tumor cell destruction. Proc Natl Acad Sci USA 2011; 108: 18342-18347
74. Brown E, Hooper L, Ho T, Gresham H. Integrin-Associated protein: a 50-kD plasma membrane antigen physically and functionally associated with integrins. J Cell Biol 1990; 111(Pt 1): 2785-2794
75. Cooper D, Lindberg FP, Gamble JR, Brown EJ, Vadas M.A. Transendothelial migration of neutrophils involves integrin-Associated protein (CD47). Proc Natl Acad Sci USA 1995; 92: 3978-3982
76. Lindberg FP, Bullard DC, Caver TE, Gresham HD, Beaudet AL, Brown EJ. Decreased resistance to bacterial infection and granulocyte defects in IAP-deficient mice. Science 1996; 274: 795-798
77. Maes H, Van Eygen S, Krysko DV, Vandenabeele P, Nys K, Rillaerts K., et al. BNIP3 supports melanoma cell migration and vasculogenic mimicry by orchestrating the actin cytoskeleton. Cell Death Dis 2014; 5: e1127
78. Bournazos S, Ravetch JV. Fcgamma receptor pathways during active and passive immunization. Immunol Rev 2015; 268: 88-103
79. Kersten K, Salvagno C, De Visser KE. Exploiting the immunomodulatory properties of chemotherapeutic drugs to improve the success of cancer immunotherapy. Front Immunol 2015; 6: 516
80. Lin TJ, Lin HT, Chang WT, Mitapalli SP, Hsiao PW, Yin SY., et al. Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components. Mol Cancer 2015; 14: 174
81. Brusa D, Garetto S, Chiorino G, Scatolini M, Migliore E, Camussi G., et al. Post-Apoptotic tumors are more palatable to dendritic cells and enhance their antigen cross-presentation activity. Vaccine 2008; 26: 6422-6432
82. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20: 197-216
83. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12: 991-1045
84. Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?. Trends Immunol 2002; 23: 445-449
85. Roux S, Apetoh L, Chalmin F, Ladoire S, Mignot G, Puig PE., et al. CD4+CD25+ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating DCs in rodent models of colon cancer. J Clin Invest 2008; 118: 3751-3761
86. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E., et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015; 520: 373-377
87. Grauer OM, Sutmuller RP, Van Maren W, Jacobs JF, Bennink E, Toonen LW., et al. Elimination of regulatory T cells is essential for an effective vaccination with tumor lysatepulsed dendritic cells in a murine glioma model. Int J Cancer 2008; 122: 1794-1802
88. Vaught DB, Cook RS. Clearance of dying cells accelerates malignancy. Oncotarget 2015; 6: 24590-24591
89. Ma Y, Aymeric L, Locher C, Mattarollo SR, Delahaye NF, Pereira P., et al. Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy. J Exp Med 2011; 208: 491-503
90. Garg AD, De Ruysscher D, Agostinis P. Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: a large-scale meta-Analysis. Oncoimmunology 2015; doi: 10.1080/2162402X.2015.1069938
91. Koks CA, Garg AD, Ehrhardt M, Riva M, Vandenberk L, Boon L., et al. Newcastle disease virotherapy induces long-term survival and tumor-specific immune memory in orthotopic glioma through the induction of immunogenic cell death. Int J Cancer 2015; 136: E313-E325
92. Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S, Knee DA., et al. Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptortargeting antibodies. J Exp Med 2013; 210: 1685-1693
93. Houot R, Kohrt HE, Marabelle A, Levy R. Targeting immune effector cells to promote antibody-induced cytotoxicity in cancer immunotherapy. Trends Immunol 2011; 32: 510-516
94. Zhao T, Ren H, Wang X, Liu P, Yan F, Jiang W., et al. Rituximab-induced HMGB1 release is associated with inhibition of STAT3 activity in human diffuse large B-cell lymphoma. Oncotarget 2015; 6: 27816-27831
95. Cheadle EJ, Sidon L, Dovedi SJ, Melis MH, Alduaij W, Illidge TM., et al. The induction of immunogenic cell death by type II anti-CD20 monoclonal antibodies has mechanistic differences compared with type I rituximab. Br J Haematol 2013; 162: 842-845
96. Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcgammaRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell 2015; 28: 285-295
97. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-264
98. Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 2015; 14: 561-584
99. Sharma P, Allison JP. The future of immune checkpoint therapy. Science 2015; 348: 56-61
100. Zappasodi R, De Braud F, Di Nicola M. Lymphoma immunotherapy: current status. Front Immunol 2015; 6: 448
101. Bellocq JP, Luporsi E, Barriere J, Bonastre J, Chetritt J, Le Corroller AG., et al. uPA/PAI-1, oncotype DX, MammaPrint((R)). Prognosis and predictive values for clinical utility in breast cancer management. Ann Pathol 2014; 34: 349-351
102. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D., et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 2004; 6: 1-6
103. Aguirre-Gamboa R, Gomez-Rueda H, Martinez-Ledesma E, Martinez-Torteya A, Chacolla-Huaringa R, Rodriguez-Barrientos A., et al. SurvExpress: an online biomarker validation tool and database for cancer gene expression data using survival analysis. PLoS One 2013; 8: e74250
104. Gyorffy B, Surowiak P, Budczies J, Lanczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One 2013; 8: e82241
105. Garg AD, Maes H, Van Vliet AR, Agostinis P. Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress. Mol Cell Oncol 2015; 2: e975089
106. Fucikova J, Moserova I, Urbanova L, Bezu L, Kepp O, Cremer I., et al. Prognostic and predictive value of DAMPs and DAMP-Associated processes in cancer. Front Immunol 2015; 6: 402
107. Van Gool S, Maes W, Ardon H, Verschuere T, Van Cauter S, De Vleeschouwer S. Dendritic cell therapy of high-grade gliomas. Brain Pathol 2009; 19: 694-712
108. Anguille S, Smits EL, Lion E, Van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol 2014; 15: e257-e267
109. Vandenberk L, Garg AD, Verschuere T, Koks C, Belmans J, Beullens M., et al. Irradiation of necrotic cancer cells employed for pulsing dendritic cells (DCs), potentiates DC vaccine-induced antitumor immunity against high-grade glioma. Oncoimmunology 2015; doi: 10.1080/2162402X.2015.1083669
110. Kepp O, Galluzzi L, Martins I, Schlemmer F, Adjemian S, Michaud M., et al. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 2011; 30: 61-69
111. Ma Y, Conforti R, Aymeric L, Locher C, Kepp O, Kroemer G., et al. How to improve the immunogenicity of chemotherapy and radiotherapy. Cancer Metastasis Rev 2011; 30: 71-82
112. Alexander HR Jr, Libutti SK, Pingpank JF, Steinberg SM, Bartlett DL, Helsabeck C., et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res 2003; 9: 6343-6349
113. Taeger G, Grabellus F, Podleska LE, Muller S, Ruchholtz S. Effectiveness of regional chemotherapy with TNF-Alpha/melphalan in advanced soft tissue sarcoma of the extremities. Int J Hyperthermia 2008; 24: 193-203
114. Stach CM, Turnay X, Voll RE, Kern PM, Kolowos W, Beyer TD., et al. Treatment with annexin V increases immunogenicity of apoptotic human T-cells in Balb/c mice. Cell Death Differ 2000; 7: 911-915
115. Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA., et al. CD47 blockade triggers T cellmediated destruction of immunogenic tumors. Nat Med 2015; 21: 1209-1215
116. Vonderheide RH. CD47 blockade as another immune checkpoint therapy for cancer. Nat Med 2015; 21: 1122-1123
117. Jinushi M, Sato M, Kanamoto A, Itoh A, Nagai S, Koyasu S., et al. Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-Autonomous and immune-mediated mechanisms. J Exp Med 2009; 206: 1317-1326
118. Dudek AM, Garg AD, Krysko DV, De Ruysscher D, Agostinis P. Inducers of immunogenic cancer cell death. Cytokine Growth Factor Rev 2013; 24: 319-333
119. Garg AD, Agostinis P. ER stress, autophagy and immunogenic cell death in photodynamic therapy-induced anti-cancer immune responses. Photochem Photobiol Sci 2014; 13: 474-487
120. Korbelik M, Zhang W, Merchant S. Involvement of damage-Associated molecular patterns in tumor response to photodynamic therapy: surface expression of calreticulin and highmobility group box-1 release. Cancer Immunol Immunother 2011; 60: 1431-1437
121. Korbelik M, Sun J, Cecic I. Photodynamic therapy-induced cell surface expression and release of heat shock proteins: relevance for tumor response. Cancer Res 2005; 65: 1018-1026
122. Bezu L, Gomes-de-Silva LC, Dewitte H, Breckpot K, Fucikova J, Spisek R., et al. Combinatorial strategies for the induction of immunogenic cell death. Front Immunol 2015; 6: 187
123. Wang Y, Yin C, Feng L, Wang C, Sheng G. Ara-C and anti-CD47 antibody combination therapy eliminates acute monocytic leukemia THP-1 cells in vivo and in vitro. Genet Mol Res 2015; 14: 5630-5641
124. Panzarini E, Inguscio V, Fimia GM, Dini L. Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release of Damage-Associated Molecular Patterns (DAMPs) in human HeLa cells. PLoS One 2014; 9: e105778
125. Shi Y, Fan X, Deng H, Brezski RJ, Rycyzyn M, Jordan RE., et al. Trastuzumab triggers phagocytic killing of high HER2 cancer cells in vitro and in vivo by interaction with Fcgamma receptors on macrophages. J Immunol 2015; 194: 4379-4386
126. Pahl JH, Kwappenberg KM, Varypataki EM, Santos SJ, Kuijjer ML, Mohamed S., et al. Macrophages inhibit human osteosarcoma cell growth after activation with the bacterial cell wall derivative liposomal muramyl tripeptide in combination with interferon-gamma. J Exp Clin Cancer Res 2014; 33: 27
127. Tipton TR, Roghanian A, Oldham RJ, Carter MJ, Cox KL, Mockridge CI., et al. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies. Blood 2015; 125: 1901-1909
128. Cheney CM, Stephens DM, Mo X, Rafiq S, Butchar J, Flynn JM., et al. Ocaratuzumab, an Fcengineered antibody demonstrates enhanced antibody-dependent cell-mediated cytotoxicity in chronic lymphocytic leukemia. mAbs 2014; 6: 749-755
129. Antoine F, Ennaciri J, Girard D. Syk is a novel target of arsenic trioxide (ATO) and is involved in the toxic effect of ATO in human neutrophils. Toxicol In Vitro 2010; 24: 936-941
130. Yang L, Brooks CR, Xiao S, Sabbisetti V, Yeung MY, Hsiao LL., et al. KIM-1-mediated phagocytosis reduces acute injury to the kidney. J Clin Invest 2015; 125: 1620-1636
131. Wolf AM, Rumpold H, Tilg H, Gastl G, Gunsilius E, Wolf D. The effect of zoledronic acid on the function and differentiation of myeloid cells. Haematologica 2006; 91: 1165-1171
132. Hyams JS, Donaldson MH, Metcalf JA, Root RK. Inhibition of human granulocyte function by methotrexate. Cancer Res 1978; 38: 650-655
133. Sheu SJ, Chao YM, Liu NC, Chan JY. Differential effects of bevacizumab, ranibizumab and aflibercept on cell viability, phagocytosis and mitochondrial bioenergetics of retinal pigment epithelial cell. Acta Ophthalmol 2015; 93: e631-e643
134. Mannerstrom M, Maenpaa H, Toimela T, Salminen L, Tahti H. The phagocytosis of rod outer segments is inhibited by selected drugs in retinal pigment epithelial cell cultures. Pharmacol Toxicol 2001; 88: 27-33
135. Kovacs P, Csaba G. Effect of drugs affecting microtubular assembly on microtubules, phospholipid synthesis and physiological indices (signalling, growth, motility and phagocytosis) in Tetrahymena pyriformis. Cell Biochem Funct 2006; 24: 419-429
136. Pallister CJ, Warnock DW. Effect of antimicrobial and antineoplastic drugs alone and in combination on the phagocytic and candidacidal function of human polymorphonuclear leucocytes. J Antimicrob Chemother 1989; 23: 87-94
137. Klettner A, Tahmaz N, Dithmer M, Richert E, Roider J. Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis. Br J Ophthalmol 2014; 98: 1448-1452
138. Denes L, Szende B, Hajos G, Szporny L, Lapis K. Selective restoration of immunosuppressive effect of cytotoxic agents by thymopoietin fragments. Cancer Immunol Immunother 1990; 32: 51-54
139. Medzihradsky JL, Wilson JG. Potentiation by thiopurines and sulfhydryl-reactive agents of the inhibition by 3-deazaadenosine of mononuclear phagocytes. Int J Immunopharmacol 1992; 14: 801-808
140. Duong MN, Matera EL, Mathe D, Evesque A, Valsesia-Wittmann S, Clemenceau B., et al. Effect of kinase inhibitors on the therapeutic properties of monoclonal antibodies. mAbs 2015; 7: 192-198
141. Kumar V, Harjai K, Chhibber S. Thalidomide treatment modulates macrophage proinflammatory function and cytokine levels in Klebsiella pneumoniae B5055 induced pneumonia in BALB/c mice. Int Immunopharmacol 2010; 10: 777-783
142. Lin JC, Liu CL, Lee JJ, Liu TP, Ko WC, Huang YC., et al. Sorafenib induces autophagy and suppresses activation of human macrophage. Int Immunopharmacol 2013; 15: 333-339
143. Lukac J, Kusic Z, Kordic D, Koncar M, Bolanca A. Natural killer cell activity, phagocytosis, and number of peripheral blood cells in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 1994; 29: 279-285
144. Dong HP, Holth A, Kleinberg L, Ruud MG, Elstrand MB, Trope CG., et al. Evaluation of cell surface expression of phosphatidylserine in ovarian carcinoma effusions using the annexin- V/7-AAD assay: clinical relevance and comparison with other apoptosis parameters. Am J Clin Pathol 2009; 132: 756-762
145. Wemeau M, Kepp O, Tesniere A, Panaretakis T, Flament C, De Botton S., et al. Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia. Cell Death Dis 2010; 1: e104
146. Eric A, Juranic Z, Milovanovic Z, Markovic I, Inic M, Stanojevic-Bakic N., et al. Effects of humoral immunity and calreticulin overexpression on postoperative course in breast cancer. Pathol Oncol Res 2009; 15: 89-90
147. Peng RQ, Chen YB, Ding Y, Zhang R, Zhang X, Yu XJ., et al. Expression of calreticulin is associated with infiltration of T-cells in stage IIIB colon cancer. World J Gastroenterol 2010; 16: 2428-2434
148. Chen CN, Chang CC, Su TE, Hsu WM, Jeng YM, Ho MC., et al. Identification of calreticulin as a prognosis marker and angiogenic regulator in human gastric cancer. Ann Surg Oncol 2009; 16: 524-533
149. Liu R, Gong J, Chen J, Li Q, Song C, Zhang J., et al. Calreticulin as a potential diagnostic biomarker for lung cancer. Cancer Immunol Immunother 2012; 61: 855-864
150. Hsu WM, Hsieh FJ, Jeng YM, Kuo ML, Chen CN, Lai DM., et al. Calreticulin expression in neuroblastoma-A novel independent prognostic factor. Ann Oncol 2005; 16: 314-321
151. Baccelli I, Stenzinger A, Vogel V, Pfitzner BM, Klein C, Wallwiener M., et al. Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients. Oncotarget 2014; 5: 8147-8160
152. Nagahara M, Mimori K, Kataoka A, Ishii H, Tanaka F, Nakagawa T., et al. Correlated expression of CD47 and SIRPA in bone marrow and in peripheral blood predicts recurrence in breast cancer patients. Clin Cancer Res 2010; 16: 4625-4635
153. Suzuki S, Yokobori T, Tanaka N, Sakai M, Sano A, Inose T., et al. CD47 expression regulated by the miR-133a tumor suppressor is a novel prognostic marker in esophageal squamous cell carcinoma. Oncol Rep 2012; 28: 465-472
154. Yoshida K, Tsujimoto H, Matsumura K, Kinoshita M, Takahata R, Matsumoto Y., et al. CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer. Cancer Med 2015; 4: 1322-1333
155. Wang H, Tan M, Zhang S, Li X, Gao J, Zhang D., et al. Expression and significance of CD44, CD47 and c-met in ovarian clear cell carcinoma. Int J Mol Sci 2015; 16: 3391-3404
156. Chen JS, Hsu YM, Chen CC, Chen LL, Lee CC, Huang TS. Secreted heat shock protein 90alpha induces colorectal cancer cell invasion through CD91/LRP-1 and NF-kappaBmediated integrin alphaV expression. J Biol Chem 2010; 285: 25458-25466
157. Galluzzi L, Bravo-San Pedro JM, Kroemer G. Organelle-specific initiation of cell death. Nat Cell Biol 2014; 16: 728-736
158. Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J., et al. Cancer cellautonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 2014; 20: 1301-1309