The secret ally: immunostimulation by anticancer drugs (original) (raw)

• 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).
  Article CAS PubMed Google Scholar
• Roussel, M. et al. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature 281, 452–455 (1979).
  Article CAS PubMed Google Scholar
• Chabner, B. A. & Roberts, T. G. Jr. Chemotherapy and the war on cancer. Nature Rev. Cancer 5, 65–72 (2005).
  Article CAS Google Scholar
• Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).
  CAS PubMed Google Scholar
• Nowell, P. & Hungerford, D. A minute chromosome in chronic granulocytic leukemia. Science 132, 1497 (1960).
  Google Scholar
• Rowley, J. D. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290–293 (1973).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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). The studies in Ref. 7 and Ref. 8 reported the molecular characterization of the transcript and protein products of the BCR–ABL gene, laying the foundations of targeted anticancer therapy.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Demetri, G. D. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347, 472–480 (2002).
  CAS PubMed Google Scholar
• Dowell, J., Minna, J. D. & Kirkpatrick, P. Erlotinib hydrochloride. Nature Rev. Drug Discov. 4, 13–14 (2005).
  Article CAS Google Scholar
• Moy, B., Kirkpatrick, P., Kar, S. & Goss, P. Lapatinib. Nature Rev. Drug Discov. 6, 431–432 (2007).
  Article CAS Google Scholar
• Blankenstein, T. The role of tumor stroma in the interaction between tumor and immune system. Curr. Opin. Immunol. 17, 180–186 (2005).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• Zitvogel, L., Apetoh, L., Ghiringhelli, F. & Kroemer, G. Immunological aspects of cancer chemotherapy. Nature Rev. Immunol. 8, 59–73 (2008).
  Article CAS Google Scholar
• Schilsky, R. L. Personalized medicine in oncology: the future is now. Nature Rev. Drug Discov. 9, 363–366 (2010).
  Article CAS Google Scholar
• Zitvogel, L., Kepp, O. & Kroemer, G. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nature Rev. Clin. Oncol. 8, 151–160 (2011).
  Article CAS Google Scholar
• Lenz, G. et al. Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med. 359, 2313–2323 (2008).
  Article CAS PubMed Google Scholar
• Nardin, A. et al. Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions. J. Invest. Dermatol. 131, 1896–1905 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Desmedt, C. et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin. Cancer Res. 14, 5158–5165 (2008).
  Article CAS PubMed Google Scholar
• Desmedt, C. et al. Multifactorial approach to predicting resistance to anthracyclines. J. Clin. Oncol. 29, 1578–1586 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39–51 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article PubMed Google Scholar
• Komohara, Y. et al. Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma. Cancer Sci. 102, 1424–1431 (2011).
  Article CAS PubMed Google Scholar
• Lee, C. H. et al. Prognostic significance of macrophage infiltration in leiomyosarcomas. Clin. Cancer Res. 14, 1423–1430 (2008).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Ladoire, S. et al. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J. Pathol. 224, 389–400 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• Hamanaka, Y. et al. Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer. Int. J. Cancer 103, 97–100 (2003).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Delahaye, N. F. et al. Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors. Nature Med. 17, 700–707 (2011). The outcome of imatinib treatment in patients with GISTs was found to be influenced by the expression pattern of alternatively spliced NKp30 isoforms, thus unveiling an immune mechanism underlying at least part of the therapeutic efficacy of imatinib.
  Article CAS PubMed Google Scholar
• Cerhan, J. R. et al. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. Blood 109, 5439–5446 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  PubMed Google Scholar
• 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). Fcγ receptors on tumour-associated leukocytes were shown to provide a dynamic platform that facilitates the monoclonal antibody-dependent activation of death receptor 5 on tumour cells, and hence their death.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Taieb, J. et al. Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J. Immunol. 176, 2722–2729 (2006).
  Article CAS PubMed Google Scholar
• Viaud, S. et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients. Cancer Res. 71, 661–665 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
• Ma, Y. et al. Contribution of IL-17-producing γδ T cells to the efficacy of anticancer chemotherapy. J. Exp. Med. 208, 491–503 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Mattarollo, S. R. et al. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res. 71, 4809–4820 (2011). The studies in Ref. 84 and Ref. 85 unravel the cellular dynamics and molecular determinants underlying the immune infiltration of experimental breast adenocarcinomas and fibrosarcomas in response to anthracycline-based chemotherapy, highlighting a crucial early role for IL-17-producing γδ T cells.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Tesniere, A. et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 29, 482–491 (2010).
  Article CAS PubMed Google Scholar
• Martins, I. et al. Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress. Oncogene 30, 1147–1158 (2011). The release of ATP by dying cancer cells, which is required for immunogenic cell death, relies on the cellular machinery for autophagy, as demonstrated in human and murine genetic models of autophagy deficiency in vitro and in vivo.
  Article CAS PubMed Google Scholar
• Obeid, M. et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nature Med. 13, 54–61 (2007). This was the first demonstration that apoptotic cell death can occur in an immunogenic fashion, provided that the endoplasmic reticulum chaperone protein calreticulin is exposed on the surface of dying cells.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• Qian, D. Z. et al. CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity. Prostate 70, 433–442 (2010).
  CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Kovarova, L. et al. Dendritic cell counts and their subsets during treatment of multiple myeloma. Neoplasma 54, 297–303 (2007).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Thomas-Schoemann, A. et al. Bystander effect of vinorelbine alters antitumor immune response. Int. J. Cancer 129, 1511–1518 (2011).
  Article CAS PubMed Google Scholar
• Purcell, W. T. & Ettinger, D. S. Novel antifolate drugs. Curr. Oncol. Rep. 5, 114–125 (2003).
  Article PubMed Google Scholar
• Gibbs, D. & Jackman, A. Pemetrexed disodium. Nature Rev. Drug Discov. 5, S16–S17 (2005).
  Article Google Scholar
• Cronstein, B. N. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol. Rev. 57, 163–172 (2005).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Monsuez, J. J., Charniot, J. C., Vignat, N. & Artigou, J. Y. Cardiac side-effects of cancer chemotherapy. Int. J. Cardiol. 144, 3–15 (2010).
  Article PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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). In the studies published in reference 107 and reference 108, patients who were simultaneously affected by lung cancer and leukaemia were treated with erlotinib or gefitinib for the first condition and experienced complete leukaemic remission; this demonstrated the existence of therapeutic off-target mechanisms ignited by EGFR inhibitors.
  Article PubMed Google Scholar
• Boehrer, S. et al. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study. Blood 111, 2170–2180 (2008).
  Article CAS PubMed Google Scholar
• Boehrer, S. et al. Erlotinib antagonizes constitutive activation of SRC family kinases and mTOR in acute myeloid leukemia. Cell Cycle 10, 3168–3175 (2011).
  Article CAS PubMed Google Scholar
• Stegmaier, K. et al. Gefitinib induces myeloid differentiation of acute myeloid leukemia. Blood 106, 2841–2848 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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). This article demonstrates that the immunostimulatory properties of imatinib (at least in part) result from a shift in the ratio between effector T cells and T reg cells; this ratio is secondary to the imatinib-mediated downregulation of indoleamine 2,3-dioxygenase in cancer cells.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Sinai, P. et al. Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo. J. Immunol. 178, 2028–2037 (2007).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Fei, F. et al. Dasatinib inhibits the proliferation and function of CD4+CD25+ regulatory T cells. Br. J. Haematol. 144, 195–205 (2009).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Weichsel, R. et al. Profound inhibition of antigen-specific T-cell effector functions by dasatinib. Clin. Cancer Res. 14, 2484–2491 (2008).
  Article CAS PubMed Google Scholar
• Schade, A. E. et al. Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood 111, 1366–1377 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Salih, J. et al. The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity. Int. J. Cancer 127, 2119–2128 (2010).
  Article CAS PubMed Google Scholar
• Nencioni, A. et al. Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation. Blood 108, 551–558 (2006).
  Article CAS PubMed Google Scholar
• Berges, C. et al. Proteasome inhibition suppresses essential immune functions of human CD4+ T cells. Immunology 124, 234–246 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Basler, M., Lauer, C., Beck, U. & Groettrup, M. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. J. Immunol. 183, 6145–6150 (2009).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS Google Scholar
• Koyasu, S. The role of PI3K in immune cells. Nature Immunol. 4, 313–319 (2003).
  Article CAS Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• Weiner, L. M., Surana, R. & Wang, S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nature Rev. Immunol. 10, 317–327 (2010). This article summarizes recent advances in the development and use of immunostimulatory monoclonal antibodies for anticancer therapy.
  Article CAS Google Scholar
• 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).
  Article CAS Google Scholar
• Zipfel, P. F. & Skerka, C. Complement regulators and inhibitory proteins. Nature Rev. Immunol. 9, 729–740 (2009).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• zum Büschenfelde, 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).
  PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• Manzoni, M. et al. Immunological effects of bevacizumab-based treatment in metastatic colorectal cancer. Oncology 79, 187–196 (2010).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Pander, J. et al. Activation of tumor-promoting type 2 macrophages by EGFR-targeting antibody cetuximab. Clin. Cancer Res. 17, 5668–5673 (2011).
  Article CAS PubMed Google Scholar
• Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Bennett, S. R. et al. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393, 478–480 (1998).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Robert, C. et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364, 2517–2526 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• Rack, B. et al. Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer. Anticancer Res. 30, 1807–1813 (2010).
  CAS PubMed Google Scholar
• Cabillic, F. et al. Aminobisphosphonate-pretreated dendritic cells trigger successful Vγ9Vδ2 T cell amplification for immunotherapy in advanced cancer patients. Cancer Immunol. Immunother. 59, 1611–1619 (2010).
  Article CAS PubMed Google Scholar
• Gyrd-Hansen, M. & Meier, P. IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer. Nature Rev. Cancer 10, 561–574 (2010).
  Article CAS Google Scholar
• Dougan, M. et al. IAP inhibitors enhance co-stimulation to promote tumor immunity. J. Exp. Med. 207, 2195–2206 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Schmudde, M. et al. Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells. Cancer Lett. 272, 110–121 (2008).
  Article CAS PubMed Google Scholar
• Lesterhuis, W. J., Haanen, J. B. & Punt, C. J. Cancer immunotherapy — revisited. Nature Rev. Drug Discov. 10, 591–600 (2011).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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). This article provides proof of principle that the propensity of tumour cells to undergo immunogenic cell death in vitro can influence the therapeutic outcome of DC-based anticancer vaccines.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• Nistico, P. et al. Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients. Int. J. Cancer 124, 130–139 (2009).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• Muraoka, D. et al. Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells. J. Immunol. 185, 3768–3776 (2010).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• Zoglmeier, C. et al. CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin. Cancer Res. 17, 1765–1775 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Yang, X. F. Factors regulating apoptosis and homeostasis of CD4+CD25highFOXP3+ regulatory T cells are new therapeutic targets. Front. Biosci. 13, 1472–1499 (2008).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Kraman, M. et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-α. Science 330, 827–830 (2010).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Zitvogel, L., Kepp, O. & Kroemer, G. Decoding cell death signals in inflammation and immunity. Cell 140, 798–804 (2010).
  Article CAS PubMed Google Scholar
• Kepp, O. et al. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev. 30, 61–69 (2011).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article Google Scholar
• Gabrilovich, D. I. Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited. Lancet Oncol. 8, 2–3 (2007).
  Article PubMed Google Scholar
• Scripture, C. D. & Figg, W. D. Drug interactions in cancer therapy. Nature Rev. Cancer 6, 546–558 (2006).
  Article CAS Google Scholar
• Marx, J. How the glucocorticoids suppress immunity. Science 270, 232–233 (1995).
  Article CAS PubMed Google Scholar
• Kubecova, M., Kolostova, K., Pinterova, D., Kacprzak, G. & Bobek, V. Cimetidine: an anticancer drug? Eur. J. Pharm. Sci. 42, 439–444 (2011).
  Article CAS PubMed Google Scholar
• Kroemer, G. & Pouyssegur, J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 13, 472–482 (2008).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Fukasawa, K. Oncogenes and tumour suppressors take on centrosomes. Nature Rev. Cancer 7, 911–924 (2007).
  Article CAS Google Scholar
• Vakkila, J. & Lotze, M. T. Inflammation and necrosis promote tumour growth. Nature Rev. Immunol. 4, 641–648 (2004).
  Article CAS Google Scholar
• Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
  Article CAS PubMed Google Scholar
• Morselli, E. et al. Oncosuppressive functions of autophagy. Antioxid. Redox Signal. 14, 2251–2269 (2011).
  Article CAS PubMed Google Scholar
• Mathew, R., Karantza-Wadsworth, V. & White, E. Role of autophagy in cancer. Nature Rev. Cancer 7, 961–967 (2007).
  Article CAS Google Scholar
• Mueller, M. M. & Fusenig, N. E. Friends or foes — bipolar effects of the tumour stroma in cancer. Nature Rev. Cancer 4, 839–849 (2004).
  Article CAS Google Scholar
• Green, D. R., Ferguson, T., Zitvogel, L. & Kroemer, G. Immunogenic and tolerogenic cell death. Nature Rev. Immunol. 9, 353–363 (2009).
  Article CAS Google Scholar
• Kepp, O., Tesniere, A., Zitvogel, L. & Kroemer, G. The immunogenicity of tumor cell death. Curr. Opin. Oncol. 21, 71–76 (2009).
  Article CAS PubMed Google Scholar
• 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). This review contains up-to-date recommendations for the functional classification of cell death subroutines, as formulated by the Nomenclature Committee on Cell Death in 2012.
• Kroemer, G. et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 16, 3–11 (2009). This review contains recommendations for the morphological classification of cell death subroutines, as formulated by the Nomenclature Committee on Cell Death in 2009.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Panaretakis, T. et al. Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J. 28, 578–590 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Martins, I. et al. Chemotherapy induces ATP release from tumor cells. Cell Cycle 8, 3723–3728 (2009).
  Article CAS PubMed Google Scholar
• Michaud, M. et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents. Science (in the press).
• Chekeni, F. B. et al. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature 467, 863–867 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, J. et al. VEGF blockade inhibits lymphocyte recruitment and ameliorates immune-mediated vascular remodeling. Circ. Res. 107, 408–417 (2010).
  Article CAS PubMed PubMed Central Google Scholar