The secret ally: Immunostimulation by anticancer drugs

Nature Reviews Drug Discovery

Volumn 11, Issue 3, 2012, Pages 215-233

  Galluzzi, Lorenzo ^a,b,c   Senovilla, Laura ^a,b,c   Zitvogel, Laurence ^a,b,c   Kroemer, Guido ^a,b,d,e  

^a Institut Gustave Roussy   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c UNIVERSITÉ PARIS SACLAY   (France)

^d HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^e UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BEVACIZUMAB; BORTEZOMIB; CARBOPLATIN; CETUXIMAB; CISPLATIN; CYCLOPHOSPHAMIDE; DACARBAZINE; DAUNORUBICIN; DOCETAXEL; DOXORUBICIN; ERLOTINIB; GEFITINIB; GEMCITABINE; GLUCOCORTICOID; IMATINIB; LAPATINIB; METHOTREXATE; MITOXANTRONE; NAVELBINE; NILOTINIB; OXALIPLATIN; PACLITAXEL; PEMETREXED; RITUXIMAB; SORAFENIB; SUNITINIB; TAXANE DERIVATIVE; UNINDEXED DRUG; VINCRISTINE;

ACUTE GRANULOCYTIC LEUKEMIA; ANTIBODY TITER; ANTINEOPLASTIC ACTIVITY; AUTOIMMUNE DISEASE; BLADDER CANCER; BREAST CANCER; CANCER IMMUNIZATION; CARCINOMA; CD8+ T LYMPHOCYTE; CHRONIC MYELOID LEUKEMIA; COLORECTAL CANCER; COLORECTAL CARCINOMA; CYTOKINE RELEASE; DENDRITIC CELL; DRUG MEGADOSE; DRUG TARGETING; GASTROINTESTINAL STROMAL TUMOR; GERM CELL TUMOR; HAIR DISEASE; HEAD AND NECK CANCER; HEAD AND NECK CARCINOMA; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; IMMUNOMODULATION; IMMUNOSTIMULATION; KAPOSI SARCOMA; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LEUKEMIA; LEUKEMIA REMISSION; LIVER CELL CARCINOMA; LIVER METASTASIS; LONG TERM SURVIVAL; LOW DRUG DOSE; LUNG CANCER; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; LYMPHOMA; MELANOMA; MERKEL CELL TUMOR; METRONOMIC DRUG ADMINISTRATION; MULTIPLE MYELOMA; NATURAL KILLER CELL; NEUROBLASTOMA; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; OVARY CARCINOMA; OVERALL SURVIVAL; PANCREAS CANCER; PERSONALIZED MEDICINE; PHILADELPHIA 1 CHROMOSOME; PLEURA MESOTHELIOMA; PREDICTIVE VALUE; PRIORITY JOURNAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; PROSTATE CANCER; REVIEW; RHEUMATOID ARTHRITIS; SARCOMA; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN DISEASE; SOFT TISSUE SARCOMA; SOLID TUMOR; SQUAMOUS CELL CARCINOMA; SURVIVAL RATE; TUMOR ASSOCIATED LEUKOCYTE;

ANIMALS; ANTIGENS, NEOPLASM; ANTINEOPLASTIC AGENTS; CANCER VACCINES; HUMANS; IMMUNIZATION; NEOPLASMS;

EID: 84857789296     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd3626     Document Type: Review

References (229)

1. Czernilofsky, A. P. et al. Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product. Nature 287, 198-203 (1980). (Pubitemid 10019765)
2. Roussel, M. et al. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature 281, 452-455 (1979). (Pubitemid 10244265)
3. Chabner, B. A. & Roberts, T. G. Jr. Chemotherapy and the war on cancer. Nature Rev. Cancer 5, 65-72 (2005). (Pubitemid 40052326)
4. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000). (Pubitemid 30046295)
5. Nowell, P. & Hungerford, D. A minute chromosome in chronic granulocytic leukemia. Science 132, 1497 (1960).
6. Rowley, J. D. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290-293 (1973).
7. Stam, K. et al. Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome. N. Engl. J. Med. 313, 1429-1433 (1985). (Pubitemid 16212323)
8. Ben-Neriah, Y., Daley, G. Q., Mes-Masson, A. M., Witte, O. N. & Baltimore, D. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science 233, 212-214 (1986). (Pubitemid 16008117)
9. Capdeville, R., Buchdunger, E., Zimmermann, J. & Matter, A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nature Rev. Drug Discov. 1, 493-502 (2002).
10. Apperley, J. F. et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor β. N. Engl. J. Med. 347, 481-487 (2002). (Pubitemid 34879335)
11. Demetri, G. D. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347, 472-480 (2002). (Pubitemid 34879334)
12. Dowell, J., Minna, J. D. & Kirkpatrick, P. Erlotinib hydrochloride. Nature Rev. Drug Discov. 4, 13-14 (2005). (Pubitemid 40109581)
13. Moy, B., Kirkpatrick, P., Kar, S. & Goss, P. Lapatinib. Nature Rev. Drug Discov. 6, 431-432 (2007). (Pubitemid 47064564)
14. Blankenstein, T. The role of tumor stroma in the interaction between tumor and immune system. Curr. Opin. Immunol. 17, 180-186 (2005). (Pubitemid 40343106)
15. Ferrara, N., Hillan, K. J., Gerber, H. P. & Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nature Rev. Drug Discov. 3, 391-400 (2004). (Pubitemid 38618122)
16. Zitvogel, L., Apetoh, L., Ghiringhelli, F. & Kroemer, G. Immunological aspects of cancer chemotherapy. Nature Rev. Immunol. 8, 59-73 (2008).
17. Schilsky, R. L. Personalized medicine in oncology: the future is now. Nature Rev. Drug Discov. 9, 363-366 (2010).
18. Zitvogel, L., Kepp, O. & Kroemer, G. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nature Rev. Clin. Oncol. 8, 151-160 (2011).
19. Lenz, G. et al. Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med. 359, 2313-2323 (2008).
20. Nardin, A. et al. Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions. J. Invest. Dermatol. 131, 1896-1905 (2011).
21. Staaf, J. et al. Identification of subtypes in human epidermal growth factor receptor 2-positive breast cancer reveals a gene signature prognostic of outcome. J. Clin. Oncol. 28, 1813-1820 (2010).
22. Thurlow, J. K. et al. Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma. J. Clin. Oncol. 28, 2881-2888 (2010).
23. Desmedt, C. et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin. Cancer Res. 14, 5158-5165 (2008).
24. Desmedt, C. et al. Multifactorial approach to predicting resistance to anthracyclines. J. Clin. Oncol. 29, 1578-1586 (2011).
25. Paulson, K. G. et al. Transcriptome-wide studies of Merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J. Clin. Oncol. 29, 1539-1546 (2011).
26. Eerola, A. K., Soini, Y. & Paakko, P. A high number of tumor-infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma. Clin. Cancer Res. 6, 1875-1881 (2000). (Pubitemid 30305084)
27. Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51 (2010).
28. Kamper, P. et al. Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin's lymphoma. Haematologica 96, 269-276 (2011).
29. Komohara, Y. et al. Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma. Cancer Sci. 102, 1424-1431 (2011).
30. Lee, C. H. et al. Prognostic significance of macrophage infiltration in leiomyosarcomas. Clin. Cancer Res. 14, 1423-1430 (2008).
31. Ding, T. et al. High tumor-infiltrating macrophage density predicts poor prognosis in patients with primary hepatocellular carcinoma after resection. Hum. Pathol. 40, 381-389 (2009).
32. Zhang, B. C. et al. Tumor-associated macrophages infiltration is associated with peritumoral lymphangiogenesis and poor prognosis in lung adenocarcinoma. Med. Oncol. 28, 1447-1452 (2010).
33. Nonomura, N. et al. Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer. BJU Int. 107, 1918-1922 (2011).
34. Kinouchi, M. et al. Infiltration of CD14-positive macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis. Hepatogastroenterology 58, 352-358 (2011).
35. Ladoire, S. et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating Foxp3+ regulatory T cells. Clin. Cancer Res. 14, 2413-2420 (2008). (Pubitemid 351551075)
36. Ladoire, S. et al. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J. Pathol. 224, 389-400 (2011).
37. De Monte, L. et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med. 208, 469-478 (2011).
38. Pedroza-Gonzalez, A. et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J. Exp. Med. 208, 479-490 (2011).
39. Fu, J. et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 132, 2328-2339 (2007). (Pubitemid 46890865)
40. Shen, Z. et al. Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer. J. Cancer Res. Clin. Oncol. 136, 1585-1595 (2010).
41. Petersen, R. P. et al. Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 107, 2866-2872 (2006). (Pubitemid 44937041)
42. Correale, P. et al. Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J. Immunother. 33, 435-441 (2010).
43. Ladoire, S., Martin, F. & Ghiringhelli, F. Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer. Cancer Immunol. Immunother. 60, 909-918 (2011).
44. Halama, N. et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 71, 5670-5677 (2011).
45. Bonertz, A. et al. Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J. Clin. Invest. 119, 3311-3321 (2009).
46. Sconocchia, G. et al. Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma. Int. J. Cancer 128, 2663-2672 (2011).
47. Alvaro-Naranjo, T. et al. Tumor-infiltrating cells as a prognostic factor in Hodgkin's lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients. Leuk. Lymphoma 46, 1581-1591 (2005). (Pubitemid 41700991)
48. Polcher, M. et al. Foxp3+ cell infiltration and granzyme B+/Foxp3+ cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol. Immunother. 59, 909-919 (2010).
49. Distel, L. V. et al. Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease. Oral Oncol. 45, e167-e174 (2009).
50. Wu, X. J. et al. Circulating antibodies to carcinoembryonic antigen related to improved recurrence-free survival of patients with colorectal carcinoma. J. Int. Med. Res. 39, 838-845 (2011).
51. Ait-Tahar, K. et al. Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk. Blood 115, 3314-3319 (2010).
52. Albertus, D. L. et al. AZGP1 autoantibody predicts survival and histone deacetylase inhibitors increase expression in lung adenocarcinoma. J. Thorac. Oncol. 3, 1236-1244 (2008).
53. Hamanaka, Y. et al. Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer. Int. J. Cancer 103, 97-100 (2003).
54. Touze, A. et al. High levels of antibodies against Merkel cell polyomavirus identify a subset of patients with Merkel cell carcinoma with better clinical outcome. J. Clin. Oncol. 29, 1612-1619 (2011).
55. Delahaye, N. F. et al. Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors. Nature Med. 17, 700-707 (2011).
56. Cerhan, J. R. et al. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. Blood 109, 5439-5446 (2007). (Pubitemid 46890567)
57. Kleinrath, T., Gassner, C., Lackner, P., Thurnher, M. & Ramoner, R. Interleukin-4 promoter polymorphisms: a genetic prognostic factor for survival in metastatic renal cell carcinoma. J. Clin. Oncol. 25, 845-851 (2007). (Pubitemid 350002885)
58. Sellick, G. S. et al. Scan of 977 nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis. Blood 111, 1625-1633 (2008). (Pubitemid 351213454)
59. Domingo-Domenech, E. et al. Impact of interleukin-10 polymorphisms (-1082 and -3575) on the survival of patients with lymphoid neoplasms. Haematologica 92, 1475-1481 (2007). (Pubitemid 350144122)
60. DeMichele, A. et al. Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer. Cancer Res. 69, 4184-4191 (2009).
61. Schoof, N. et al. Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial. Ann. Oncol. 20, 1548-1554 (2009).
62. Bibeau, F. et al. Impact of FcγRIIa-FcγRIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J. Clin. Oncol. 27, 1122-1129 (2009).
63. Ferris, R. L., Jaffee, E. M. & Ferrone, S. Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J. Clin. Oncol. 28, 4390-4399 (2010).
64. Wang, B., Kokhaei, P., Mellstedt, H. & Liljefors, M. FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment. Int. J. Oncol. 37, 1599-1606 (2010).
65. Wilson, N. S. et al. An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19, 101-113 (2011).
66. Menard, C. et al. Natural killer cell IFN-γ levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res. 69, 3563-3569 (2009).
67. Gulley, J. L. et al. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol. Immunother. 59, 663-674 (2010).
68. Liu, W. M., Fowler, D. W., Smith, P. & Dalgleish, A. G. Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses. Br. J. Cancer 102, 115-123 (2010).
69. Nowak, A. K. et al. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J. Immunol. 170, 4905-4913 (2003). (Pubitemid 36554719)
70. Nowak, A. K., Robinson, B. W. & Lake, R. A. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res. 63, 4490-4496 (2003). (Pubitemid 36951021)
71. Mundy-Bosse, B. L. et al. Myeloid-derived suppressor cell inhibition of the IFN response in tumor-bearing mice. Cancer Res. 71, 5101-5110 (2011).
72. Vincent, J. et al. 5-fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 70, 3052-3061 (2010).
73. Lesterhuis, W. J. et al. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J. Clin. Invest. 121, 3100-3108 (2011).
74. Weiner, H. L. & Cohen, J. A. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Mult. Scler. 8, 142-154 (2002). (Pubitemid 34256752)
75. Medina-Echeverz, J. et al. Successful colon cancer eradication after chemoimmunotherapy is associated with profound phenotypic change of intratumoral myeloid cells. J. Immunol. 186, 807-815 (2011).
76. Ghiringhelli, F. et al. 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, 641-648 (2007). (Pubitemid 46348738)
77. Taieb, J. et al. Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J. Immunol. 176, 2722-2729 (2006).
78. Viaud, S. et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients. Cancer Res. 71, 661-665 (2011).
79. Schiavoni, G. et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 71, 768-778 (2011).
80. Guerriero, J. L. et al. DNA alkylating therapy induces tumor regression through an HMGB1-mediated activation of innate immunity. J. Immunol. 186, 3517-3526 (2011).
81. Hirschhorn-Cymerman, D. et al. OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis. J. Exp. Med. 206, 1103-1116 (2009).
82. Diaz-Montero, C. M. et al. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol. Immunother. 58, 49-59 (2009).
83. Ge, Y. et al. Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol. Immunother. 14 Sep 2011(doi:10.1007/s00262-011-1106-3).
84. Ma, Y. et al. Contribution of IL-17-producing γ? T cells to the efficacy of anticancer chemotherapy. J. Exp. Med. 208, 491-503 (2011).
85. Mattarollo, S. R. et al. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res. 71, 4809-4820 (2011).
86. Haggerty, T. J. et al. Topoisomerase inhibitors modulate expression of melanocytic antigens and enhance T cell recognition of tumor cells. Cancer Immunol. Immunother. 60, 133-144 (2011).
87. Tesniere, A. et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 29, 482-491 (2010).
88. Martins, I. et al. Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress. Oncogene 30, 1147-1158 (2011).
89. Obeid, M. et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nature Med. 13, 54-61 (2007). (Pubitemid 46067386)
90. Vitale, I., Galluzzi, L., Castedo, M. & Kroemer, G. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nature Rev. Mol. Cell Biol. 12, 385-392 (2011).
91. Zhu, Y., Liu, N., Xiong, S. D., Zheng, Y. J. & Chu, Y. W. CD4+Foxp3+ regulatory T-cell impairment by paclitaxel is independent of toll-like receptor 4. Scand. J. Immunol. 73, 301-308 (2011).
92. Ramakrishnan, R. et al. Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. J. Clin. Invest. 120, 1111-1124 (2010).
93. Kodumudi, K. N. et al. A novel chemoimmunomodulating property of docetaxel: suppression of myeloid-derived suppressor cells in tumor bearers. Clin. Cancer Res. 16, 4583-4594 (2010).
94. Niiya, M. et al. Induction of TNF-α, uPA, IL-8 and MCP-1 by doxorubicin in human lung carcinoma cells. Cancer Chemother. Pharmacol. 52, 391-398 (2003). (Pubitemid 37363612)
95. Geller, M. A., Bui-Nguyen, T. M., Rogers, L. M. & Ramakrishnan, S. Chemotherapy induces macrophage chemoattractant protein-1 production in ovarian cancer. Int. J. Gynecol. Cancer 20, 918-925 (2010).
96. Qian, D. Z. et al. CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity. Prostate 70, 433-442 (2010).
97. Fujimoto, H. et al. Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression. Int. J. Cancer 125, 1276-1284 (2009).
98. Kovarova, L. et al. Dendritic cell counts and their subsets during treatment of multiple myeloma. Neoplasma 54, 297-303 (2007).
99. Shurin, G. V., Tourkova, I. L., Kaneno, R. & Shurin, M. R. Chemotherapeutic agents in noncytotoxic concentrations increase antigen presentation by dendritic cells via an IL-12-dependent mechanism. J. Immunol. 183, 137-144 (2009).
100. Thomas-Schoemann, A. et al. Bystander effect of vinorelbine alters antitumor immune response. Int. J. Cancer 129, 1511-1518 (2011).
101. Purcell, W. T. & Ettinger, D. S. Novel antifolate drugs. Curr. Oncol. Rep. 5, 114-125 (2003). (Pubitemid 38898774)
102. Gibbs, D. & Jackman, A. Pemetrexed disodium. Nature Rev. Drug Discov. 5, S16-S17 (2005). (Pubitemid 40674340)
103. Cronstein, B. N. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol. Rev. 57, 163-172 (2005). (Pubitemid 41043882)
104. Kaneno, R., Shurin, G. V., Tourkova, I. L. & Shurin, M. R. Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations. J. Transl. Med. 7, 58 (2009).
105. Hartmann, J. T., Haap, M., Kopp, H. G. & Lipp, H. P. Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr. Drug Metab. 10, 470-481 (2009).
106. Monsuez, J. J., Charniot, J. C., Vignat, N. & Artigou, J. Y. Cardiac side-effects of cancer chemotherapy. Int. J. Cardiol. 144, 3-15 (2010).
107. Chan, G. & Pilichowska, M. Complete remission in a patient with acute myelogenous leukemia treated with erlotinib for non small-cell lung cancer. Blood 110, 1079-1080 (2007). (Pubitemid 47267456)
108. Pitini, V., Arrigo, C. & Altavilla, G. Erlotinib in a patient with acute myelogenous leukemia and concomitant non-small-cell lung cancer. J. Clin. Oncol. 26, 3645-3646 (2008).
109. Boehrer, S. et al. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study. Blood 111, 2170-2180 (2008). (Pubitemid 351451531)
110. Boehrer, S. et al. Erlotinib antagonizes constitutive activation of SRC family kinases and mTOR in acute myeloid leukemia. Cell Cycle 10, 3168-3175 (2011).
111. Stegmaier, K. et al. Gefitinib induces myeloid differentiation of acute myeloid leukemia. Blood 106, 2841-2848 (2005). (Pubitemid 41510762)
112. Pollack, B. P., Sapkota, B. & Cartee, T. V. Epidermal growth factor receptor inhibition augments the expression of MHC class I and II genes. Clin. Cancer Res. 17, 4400-4413 (2011).
113. Garrido, G. et al. Induction of immunogenic apoptosis by blockade of epidermal growth factor receptor activation with a specific antibody. J. Immunol. 187, 4954-4966 (2011).
114. Luo, Q. et al. Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf/ERK cascade and Akt signaling pathway. Toxicol. Appl. Pharmacol. 251, 130-136 (2011).
115. Chen, C. I., Maecker, H. T. & Lee, P. P. Development and dynamics of robust T-cell responses to CML under imatinib treatment. Blood 111, 5342-5349 (2008).
116. Catellani, S., Pierri, I., Gobbi, M., Poggi, A. & Zocchi, M. R. Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia. PLoS ONE 6, e18925 (2011).
117. Larmonier, N. et al. Imatinib mesylate inhibits CD4+CD25+ regulatory T cell activity and enhances active immunotherapy against BCR-ABL- tumors. J. Immunol. 181, 6955-6963 (2008).
118. Balachandran, V. P. et al. Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido. Nature Med. 17, 1094-1100 (2011).
119. Gao, H. et al. Imatinib mesylate suppresses cytokine synthesis by activated CD4 T cells of patients with chronic myelogenous leukemia. Leukemia 19, 1905-1911 (2005). (Pubitemid 41553998)
120. Seggewiss, R. et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood 105, 2473-2479 (2005). (Pubitemid 40387048)
121. Leder, C., Ortler, S., Seggewiss, R., Einsele, H. & Wiendl, H. Modulation of T-effector function by imatinib at the level of cytokine secretion. Exp. Hematol. 35, 1266-1271 (2007). (Pubitemid 47088775)
122. Sinai, P. et al. Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo. J. Immunol. 178, 2028-2037 (2007). (Pubitemid 46233399)
123. Adotevi, O. et al. 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 (2010).
124. Ko, J. S. et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin. Cancer Res. 15, 2148-2157 (2009).
125. Finke, J. H. et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin. Cancer Res. 14, 6674-6682 (2008).
126. Desar, I. M. et al. Sorafenib reduces the percentage of tumour infiltrating regulatory T cells in renal cell carcinoma patients. Int. J. Cancer 129, 507-512 (2011).
127. Xin, H. et al. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 69, 2506-2513 (2009).
128. Dalton, J. E. et al. Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice. J. Clin. Invest. 120, 1204-1216 (2010).
129. Hipp, M. M. et al. Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood 111, 5610-5620 (2008).
130. Fei, F. et al. Dasatinib inhibits the proliferation and function of CD4+CD25+ regulatory T cells. Br. J. Haematol. 144, 195-205 (2009).
131. Fei, F. et al. Dasatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral and leukemia antigens. Exp. Hematol. 36, 1297-1308 (2008).
132. Weichsel, R. et al. Profound inhibition of antigen-specific T-cell effector functions by dasatinib. Clin. Cancer Res. 14, 2484-2491 (2008). (Pubitemid 351551084)
133. Schade, A. E. et al. Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood 111, 1366-1377 (2008). (Pubitemid 351213423)
134. Fraser, C. K. et al. Dasatinib inhibits recombinant viral antigen-specific murine CD4+ and CD8+ T-cell responses and NK-cell cytolytic activity in vitro and in vivo. Exp. Hematol. 37, 256-265 (2009).
135. Fraser, C. K. et al. Dasatinib inhibits the secretion of TNF-α following TLR stimulation in vitro and in vivo. Exp. Hematol. 37, 1435-1444 (2009).
136. Blake, S., Hughes, T. P., Mayrhofer, G. & Lyons, A. B. The Src/ABL kinase inhibitor dasatinib (BMS-354825) inhibits function of normal human T-lymphocytes in vitro. Clin. Immunol. 127, 330-339 (2008).
137. Chen, J. et al. Nilotinib hampers the proliferation and function of CD8+ T lymphocytes through inhibition of T cell receptor signalling. J. Cell. Mol. Med. 12, 2107-2118 (2008).
138. Salih, J. et al. The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity. Int. J. Cancer 127, 2119-2128 (2010).
139. Nencioni, A. et al. Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation. Blood 108, 551-558 (2006). (Pubitemid 44061355)
140. Berges, C. et al. Proteasome inhibition suppresses essential immune functions of human CD4+ T cells. Immunology 124, 234-246 (2008). (Pubitemid 351692904)
141. Basler, M., Lauer, C., Beck, U. & Groettrup, M. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. J. Immunol. 183, 6145-6150 (2009).
142. Heider, U. et al. Decrease in CD4+ T-cell counts in patients with multiple myeloma treated with bortezomib. Clin. Lymphoma Myeloma Leuk. 10, 134-137 (2010).
143. Blanco, B. et al. Treatment with bortezomib of human CD4+ T cells preserves natural regulatory T cells and allows the emergence of a distinct suppressor T-cell population. Haematologica 94, 975-983 (2009).
144. Liu, P., Cheng, H., Roberts, T. M. & Zhao, J. J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nature Rev. Drug Discov. 8, 627-644 (2009).
145. Koyasu, S. The role of PI3K in immune cells. Nature Immunol. 4, 313-319 (2003).
146. Carrington, E. M. et al. BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs. Proc. Natl Acad. Sci. USA 107, 10967-10971 (2010).
147. Weiner, L. M., Surana, R. & Wang, S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nature Rev. Immunol. 10, 317-327 (2010).
148. Winiarska, M., Glodkowska-Mrowka, E., Bil, J. & Golab, J. Molecular mechanisms of the antitumor effects of anti-CD20 antibodies. Front. Biosci. 16, 277-306 (2011).
149. Zipfel, P. F. & Skerka, C. Complement regulators and inhibitory proteins. Nature Rev. Immunol. 9, 729-740 (2009).
150. Marechal, R. et al. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. BMC Cancer 10, 340 (2010).
151. Banerjee, D. et al. Enhanced T-cell responses to glioma cells coated with the anti-EGF receptor antibody and targeted to activating FcγRs on human dendritic cells. J. Immunother. 31, 113-120 (2008).
152. zum Bschenfelde, C. M., Hermann, C., Schmidt, B., Peschel, C. & Bernhard, H. Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2-overexpressing tumor cells. Cancer Res. 62, 2244-2247 (2002). (Pubitemid 34411698)
153. Arnould, L. et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br. J. Cancer 94, 259-267 (2006). (Pubitemid 43151545)
154. Wada, J. et al. The contribution of vascular endothelial growth factor to the induction of regulatory T-cells in malignant effusions. Anticancer Res. 29, 881-888 (2009).
155. Manzoni, M. et al. Immunological effects of bevacizumab-based treatment in metastatic colorectal cancer. Oncology 79, 187-196 (2010).
156. Osada, T. et al. The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients. Cancer Immunol. Immunother. 57, 1115-1124 (2008).
157. Shrimali, R. K. et al. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 70, 6171-6180 (2010).
158. Pander, J. et al. Activation of tumor-promoting type 2 macrophages by EGFR-targeting antibody cetuximab. Clin. Cancer Res. 17, 5668-5673 (2011).
159. Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711-723 (2010).
160. Kline, J. & Gajewski, T. F. Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Curr. Opin. Investig. Drugs 11, 1354-1359 (2010).
161. Fourcade, J. et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J. Exp. Med. 207, 2175-2186 (2010).
162. Bennett, S. R. et al. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393, 478-480 (1998).
163. Sakuishi, K. et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J. Exp. Med. 207, 2187-2194 (2010).
164. Wang, W. et al. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+CD25Hi regulatory T cells. Int. Immunol. 21, 1065-1077 (2009).
165. Yuan, J. et al. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc. Natl Acad. Sci. USA 105, 20410-20415 (2008).
166. Beatty, G. L. et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331, 1612-1616 (2011).
167. Jiang, Q. et al. mTOR kinase inhibitor AZD8055 enhances the immunotherapeutic activity of an agonist CD40 antibody in cancer treatment. Cancer Res. 71, 4074-4084 (2011).
168. Robert, C. et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364, 2517-2526 (2011).
169. Norton, J. T., Hayashi, T., Crain, B., Corr, M. & Carson, D. A. Role of IL-1 receptor-associated kinase-M (IRAK-M) in priming of immune and inflammatory responses by nitrogen bisphosphonates. Proc. Natl Acad. Sci. USA 108, 11163-11168 (2011).
170. Rack, B. et al. Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer. Anticancer Res. 30, 1807-1813 (2010).
171. Cabillic, F. et al. Aminobisphosphonate-pretreated dendritic cells trigger successful Vγ9V2 T cell amplification for immunotherapy in advanced cancer patients. Cancer Immunol. Immunother. 59, 1611-1619 (2010).
172. Gyrd-Hansen, M. & Meier, P. IAPs: from caspase inhibitors to
173. Dougan, M. et al. IAP inhibitors enhance co-stimulation to promote tumor immunity. J. Exp. Med. 207, 2195-2206 (2010).
174. Schmudde, M. et al. Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells. Cancer Lett. 272, 110-121 (2008).
175. Lesterhuis, W. J., Haanen, J. B. & Punt, C. J. Cancer immunotherapy - revisited. Nature Rev. Drug Discov. 10, 591-600 (2011).
176. Emens, L. A. et al. 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 (2009).
177. Arlen, P. M. et al. A randomized Phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin. Cancer Res. 12, 1260-1269 (2006). (Pubitemid 43342517)
178. Garnett, C. T., Schlom, J. & Hodge, J. W. Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin. Cancer Res. 14, 3536-3544 (2008).
179. Lesterhuis, W. J. et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br. J. Cancer 103, 1415-1421 (2010).
180. Narita, M. et al. WT1 peptide vaccination in combination with imatinib therapy for a patient with CML in the chronic phase. Int. J. Med. Sci. 7, 72-81 (2010).
181. Gonzalez-Aparicio, M. et al. Oxaliplatin in combination with liver-specific expression of interleukin 12 reduces the immunosuppressive microenvironment of tumours and eradicates metastatic colorectal cancer in mice. Gut 60, 341-349 (2011).
182. Zappasodi, R. et al. Improved clinical outcome in indolent B-cell lymphoma patients vaccinated with autologous tumor cells experiencing immunogenic death. Cancer Res. 70, 9062-9072 (2010).
183. Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A. & Dudley, M. E. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nature Rev. Cancer 8, 299-308 (2008). (Pubitemid 351430867)
184. Nistico, P. et al. Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients. Int. J. Cancer 124, 130-139 (2009).
185. Palermo, B. et al. Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of melan-A-specific, tumor-reactive CTL in melanoma patients. Cancer Res. 70, 7084-7092 (2010).
186. Kyte, J. A. et al. Telomerase peptide vaccination combined with temozolomide: a clinical trial in stage IV melanoma patients. Clin. Cancer Res. 17, 4568-4580 (2011).
187. Rettig, L. et al. Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells. Int. J. Cancer 129, 832-838 (2011).
188. Adams, S. et al. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J. Immunol. 181, 776-784 (2008).
189. Davis, I. D. et al. Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients. J. Immunother. 29, 499-511 (2006). (Pubitemid 44395275)
190. Robbins, P. F. et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 29, 917-924 (2011).
191. Muraoka, D. et al. Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells. J. Immunol. 185, 3768-3776 (2010).
192. Bourquin, C., Schreiber, S., Beck, S., Hartmann, G. & Endres, S. Immunotherapy with dendritic cells and CpG oligonucleotides can be combined with chemotherapy without loss of efficacy in a mouse model of colon cancer. Int. J. Cancer 118, 2790-2795 (2006). (Pubitemid 43673358)
193. Brody, J. D. et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28, 4324-4332 (2010).
194. Zoglmeier, C. et al. CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin. Cancer Res. 17, 1765-1775 (2011).
195. Wang, Y., Wang, X. Y., Subjeck, J. R., Shrikant, P. A. & Kim, H. L. Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. Br. J. Cancer 104, 643-652 (2011).
196. Yang, X. F. Factors regulating apoptosis and homeostasis of CD4+CD25highFOXP3+ regulatory T cells are new therapeutic targets. Front. Biosci. 13, 1472-1499 (2008).
197. Yu, H., Kortylewski, M. & Pardoll, D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Rev. Immunol. 7, 41-51 (2007). (Pubitemid 46020826)
198. Schust, J., Sperl, B., Hollis, A., Mayer, T. U. & Berg, T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem. Biol. 13, 1235-1242 (2006). (Pubitemid 44750735)
199. Kraman, M. et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-α. Science 330, 827-830 (2010).
200. Shields, J. D., Kourtis, I. C., Tomei, A. A., Roberts, J. M. & Swartz, M. A. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 328, 749-752 (2010).
201. Schietinger, A., Philip, M., Liu, R. B., Schreiber, K. & Schreiber, H. Bystander killing of cancer requires the cooperation of CD4+ and CD8+ T cells during the effector phase. J. Exp. Med. 207, 2469-2477 (2010).
202. Zitvogel, L., Kepp, O. & Kroemer, G. Decoding cell death signals in inflammation and immunity. Cell 140, 798-804 (2010).
203. Kepp, O. et al. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev. 30, 61-69 (2011).
204. Rakhra, K. et al. CD4+ T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485-498 (2010).
205. Chakraborty, M. et al. The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing. Clin. Cancer Res. 14, 4241-4249 (2008).
206. Lynch, T. et al. Phase II trial of ipilimumab (IPI) and paclitaxel/carboplatin (P/C) in first-line stage IIIb/IV non-small cell lung cancer (NSCLC). J. Clin. Oncol. (Meeting Abstracts) 28, 7531 (2010).
207. Gabrilovich, D. I. Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited. Lancet Oncol. 8, 2-3 (2007). (Pubitemid 44943085)
208. Scripture, C. D. & Figg, W. D. Drug interactions in cancer therapy. Nature Rev. Cancer 6, 546-558 (2006). (Pubitemid 43980543)
209. Marx, J. How the glucocorticoids suppress immunity. Science 270, 232-233 (1995).
210. Kubecova, M., Kolostova, K., Pinterova, D., Kacprzak, G. & Bobek, V. Cimetidine: an anticancer drug? Eur. J. Pharm. Sci. 42, 439-444 (2011).
211. Kroemer, G. & Pouyssegur, J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 13, 472-482 (2008). (Pubitemid 351766797)
212. Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331, 1565-1570 (2011).
213. Fukasawa, K. Oncogenes and tumour suppressors take on centrosomes. Nature Rev. Cancer 7, 911-924 (2007). (Pubitemid 350165854)
214. Vakkila, J. & Lotze, M. T. Inflammation and necrosis promote tumour growth. Nature Rev. Immunol. 4, 641-648 (2004). (Pubitemid 39025049)
215. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646-674 (2011).
216. Morselli, E. et al. Oncosuppressive functions of autophagy. Antioxid. Redox Signal. 14, 2251-2269 (2011).
217. Mathew, R., Karantza-Wadsworth, V. & White, E. Role of autophagy in cancer. Nature Rev. Cancer 7, 961-967 (2007). (Pubitemid 350165856)
218. Mueller, M. M. & Fusenig, N. E. Friends or foes - bipolar effects of the tumour stroma in cancer. Nature Rev. Cancer 4, 839-849 (2004). (Pubitemid 39472951)
219. Green, D. R., Ferguson, T., Zitvogel, L. & Kroemer, G. Immunogenic and tolerogenic cell death. Nature Rev. Immunol. 9, 353-363 (2009).
220. Kepp, O., Tesniere, A., Zitvogel, L. & Kroemer, G. The immunogenicity of tumor cell death. Curr. Opin. Oncol. 21, 71-76 (2009).
221. Galluzzi, L. et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 15 Jul 2011 (doi:10.1038/cdd.2011.96).
222. Kroemer, G. et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 16, 3-11 (2009).
223. Apetoh, L. et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature Med. 13, 1050-1059 (2007). (Pubitemid 47517504)
224. Ghiringhelli, F. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nature Med. 15, 1170-1178 (2009).
225. Panaretakis, T. et al. Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J. 28, 578-590 (2009).
226. Martins, I. et al. Chemotherapy induces ATP release from tumor cells. Cell Cycle 8, 3723-3728 (2009).
227. Michaud, M. et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents. Science (in the press).
228. Chekeni, F. B. et al. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature 467, 863-867 (2010).
229. Zhang, J. et al. VEGF blockade inhibits lymphocyte recruitment and ameliorates immune-mediated vascular remodeling. Circ. Res. 107, 408-417 (2010).