Home LiteratureArticle Details
PMID: 22301798 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

The secret ally: immunostimulation by anticancer drugs.

Nature reviews. Drug discovery ·Vol. 11 ·No. 3 ·2012-02-03 ·Pages 215-33

Galluzzi L, Senovilla L, Zitvogel L, Kroemer G

Abstract

It has recently become clear that the tumour microenvironment, and in particular the immune system, has a crucial role in modulating tumour progression and response to therapy. Indicators of an ongoing immune response, such as the composition of the intratumoural immune infiltrate, as well as polymorphisms in genes encoding immune modulators, have been correlated with therapeutic outcome. Moreover, several anticancer agents--including classical chemotherapeutics and targeted compounds--stimulate tumour-specific immune responses either by inducing the immunogenic death of tumour cells or by engaging immune effector mechanisms. Here, we discuss the molecular and cellular circuitries whereby cytotoxic agents can activate the immune system against cancer, and their therapeutic implications.

MeSH Terms
Animals Antigens, Neoplasm/immunology Antineoplastic Agents/pharmacology,therapeutic use Cancer Vaccines/immunology,therapeutic use Humans Immunization/methods,trends Neoplasms/drug therapy,immunology,prevention & control
Chemicals
Antigens, Neoplasm Antineoplastic Agents Cancer Vaccines
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Galluzzi Lorenzo
INSERM U848, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F-94805 Villejuif, France.
Senovilla Laura
Zitvogel Laurence
Kroemer Guido
References (225)
225 references, click to expand
  1. Targeting the phosphoinositide 3-kinase pathway in cancer.
    Nat Rev Drug Discov. 2009 Aug;8(8):627-44 PMID: 19644473
  2. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?
    Br J Cancer. 2006 Jan 30;94(2):259-67 PMID: 16404427
  3. Scan of 977 nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis.
    Blood. 2008 Feb 1;111(3):1625-33 PMID: 18006695
  4. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients.
    Br J Cancer. 2010 Oct 26;103(9):1415-21 PMID: 20924373
  5. Chemotherapeutic agents in noncytotoxic concentrations increase antigen presentation by dendritic cells via an IL-12-dependent mechanism.
    J Immunol. 2009 Jul 1;183(1):137-44 PMID: 19535620
  6. Immunological aspects of cancer chemotherapy.
    Nat Rev Immunol. 2008 Jan;8(1):59-73 PMID: 18097448
  7. Lapatinib.
    Nat Rev Drug Discov. 2007 Jun;6(6):431-2 PMID: 17633789
  8. Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy.
    J Immunother. 2010 May;33(4):435-41 PMID: 20386463
  9. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation.
    Nature. 1979 Oct 11;281(5731):452-5 PMID: 226888
  10. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21.
    Science. 2010 May 7;328(5979):749-52 PMID: 20339029
  11. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion.
    Science. 2011 Mar 25;331(6024):1565-70 PMID: 21436444
  12. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer.
    Nat Rev Cancer. 2010 Aug;10(8):561-74 PMID: 20651737
  13. Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression.
    Int J Cancer. 2009 Sep 15;125(6):1276-84 PMID: 19479998
  14. Nilotinib hampers the proliferation and function of CD8+ T lymphocytes through inhibition of T cell receptor signalling.
    J Cell Mol Med. 2008 Oct;12(5B):2107-18 PMID: 18194453
  15. Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation.
    Blood. 2006 Jul 15;108(2):551-8 PMID: 16537813
  16. A novel chemoimmunomodulating property of docetaxel: suppression of myeloid-derived suppressor cells in tumor bearers.
    Clin Cancer Res. 2010 Sep 15;16(18):4583-94 PMID: 20702612
  17. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.
    Science. 2011 Mar 25;331(6024):1612-6 PMID: 21436454
  18. FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment.
    Int J Oncol. 2010 Dec;37(6):1599-606 PMID: 21042730
  19. Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma.
    J Clin Invest. 2009 Nov;119(11):3311-21 PMID: 19809157
  20. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis.
    Nature. 2010 Oct 14;467(7317):863-7 PMID: 20944749
  21. Friends or foes - bipolar effects of the tumour stroma in cancer.
    Nat Rev Cancer. 2004 Nov;4(11):839-49 PMID: 15516957
  22. Dendritic cell counts and their subsets during treatment of multiple myeloma.
    Neoplasma. 2007;54(4):297-303 PMID: 17822319
  23. The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing.
    Clin Cancer Res. 2008 Jul 1;14(13):4241-9 PMID: 18594006
  24. 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. 2010 Jun 10;28(17):2881-8 PMID: 20458058
  25. WT1 peptide vaccination in combination with imatinib therapy for a patient with CML in the chronic phase.
    Int J Med Sci. 2010 Apr 20;7(2):72-81 PMID: 20428337
  26. Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan.
    J Clin Oncol. 2009 Mar 1;27(7):1122-9 PMID: 19164213
  27. Complement regulators and inhibitory proteins.
    Nat Rev Immunol. 2009 Oct;9(10):729-40 PMID: 19730437
  28. Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
    Nature. 1998 Jun 4;393(6684):478-80 PMID: 9624004
  29. Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions.
    J Invest Dermatol. 2011 Sep;131(9):1896-905 PMID: 21654834
  30. Macrophage diversity enhances tumor progression and metastasis.
    Cell. 2010 Apr 2;141(1):39-51 PMID: 20371344
  31. Hallmarks of cancer: the next generation.
    Cell. 2011 Mar 4;144(5):646-74 PMID: 21376230
  32. 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. 2010 Apr 22;115(16):3314-9 PMID: 20185586
  33. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells.
    Int Immunol. 2009 Sep;21(9):1065-77 PMID: 19651643
  34. 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. 2009 Dec 10;27(35):5911-8 PMID: 19805669
  35. Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer.
    Cancer Res. 2009 May 15;69(10):4184-91 PMID: 19435922
  36. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes.
    Clin Cancer Res. 2008 Aug 15;14(16):5158-65 PMID: 18698033
  37. Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients.
    J Immunother. 2006 Sep-Oct;29(5):499-511 PMID: 16971806
  38. High tumor-infiltrating macrophage density predicts poor prognosis in patients with primary hepatocellular carcinoma after resection.
    Hum Pathol. 2009 Mar;40(3):381-9 PMID: 18992916
  39. Activation of tumor-promoting type 2 macrophages by EGFR-targeting antibody cetuximab.
    Clin Cancer Res. 2011 Sep 1;17(17):5668-73 PMID: 21788356
  40. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1.
    J Clin Oncol. 2011 Mar 1;29(7):917-24 PMID: 21282551
  41. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice.
    Science. 2011 Dec 16;334(6062):1573-7 PMID: 22174255
  42. Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo.
    J Immunol. 2007 Feb 15;178(4):2028-37 PMID: 17277106
  43. Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells.
    J Immunol. 2010 Sep 15;185(6):3768-76 PMID: 20733202
  44. Decoding cell death signals in inflammation and immunity.
    Cell. 2010 Mar 19;140(6):798-804 PMID: 20303871
  45. Inflammation and necrosis promote tumour growth.
    Nat Rev Immunol. 2004 Aug;4(8):641-8 PMID: 15286730
  46. Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress.
    Oncogene. 2011 Mar 10;30(10):1147-58 PMID: 21151176
  47. Immunological effects of bevacizumab-based treatment in metastatic colorectal cancer.
    Oncology. 2010;79(3-4):187-96 PMID: 21358206
  48. AZGP1 autoantibody predicts survival and histone deacetylase inhibitors increase expression in lung adenocarcinoma.
    J Thorac Oncol. 2008 Nov;3(11):1236-44 PMID: 18978557
  49. Improved survival with ipilimumab in patients with metastatic melanoma.
    N Engl J Med. 2010 Aug 19;363(8):711-23 PMID: 20525992
  50. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer.
    Clin Cancer Res. 2006 Feb 15;12(4):1260-9 PMID: 16489082
  51. Erlotinib in a patient with acute myelogenous leukemia and concomitant non-small-cell lung cancer.
    J Clin Oncol. 2008 Jul 20;26(21):3645-6 PMID: 18640945
  52. Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy.
    J Exp Med. 2011 Mar 14;208(3):491-503 PMID: 21383056
  53. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene.
    Science. 1986 Jul 11;233(4760):212-4 PMID: 3460176
  54. 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. 2009 Jul;94(7):975-83 PMID: 19508976
  55. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining.
    Nature. 1973 Jun 1;243(5405):290-3 PMID: 4126434
  56. The immunogenicity of tumor cell death.
    Curr Opin Oncol. 2009 Jan;21(1):71-6 PMID: 19125021
  57. Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations.
    J Transl Med. 2009 Jul 10;7:58 PMID: 19591684
  58. The Src/ABL kinase inhibitor dasatinib (BMS-354825) inhibits function of normal human T-lymphocytes in vitro.
    Clin Immunol. 2008 Jun;127(3):330-9 PMID: 18395492
  59. Development and dynamics of robust T-cell responses to CML under imatinib treatment.
    Blood. 2008 Jun 1;111(11):5342-9 PMID: 18326818
  60. Chemotherapy induces macrophage chemoattractant protein-1 production in ovarian cancer.
    Int J Gynecol Cancer. 2010 Aug;20(6):918-25 PMID: 20683396
  61. Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma.
    Cancer Sci. 2011 Jul;102(7):1424-31 PMID: 21453387
  62. Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product.
    Nature. 1980 Sep 18;287(5779):198-203 PMID: 6253794
  63. Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement.
    Clin Cancer Res. 2008 Jun 1;14(11):3536-44 PMID: 18519787
  64. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors.
    Cancer Res. 2003 Aug 1;63(15):4490-6 PMID: 12907622
  65. Cancer immunotherapy--revisited.
    Nat Rev Drug Discov. 2011 Aug 01;10(8):591-600 PMID: 21804596
  66. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner.
    Blood. 2005 Mar 15;105(6):2473-9 PMID: 15572591
  67. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.
    Nat Med. 2009 Oct;15(10):1170-8 PMID: 19767732
  68. Adoptive cell transfer: a clinical path to effective cancer immunotherapy.
    Nat Rev Cancer. 2008 Apr;8(4):299-308 PMID: 18354418
  69. Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines.
    Br J Cancer. 2011 Feb 15;104(4):643-52 PMID: 21285988
  70. Circulating antibodies to carcinoembryonic antigen related to improved recurrence-free survival of patients with colorectal carcinoma.
    J Int Med Res. 2011;39(3):838-45 PMID: 21819716
  71. Pemetrexed disodium.
    Nat Rev Drug Discov. 2005 May;Suppl:S16-7 PMID: 15962527
  72. Complete remission in a patient with acute myelogenous leukemia treated with erlotinib for non small-cell lung cancer.
    Blood. 2007 Aug 1;110(3):1079-80 PMID: 17644748
  73. Interleukin-4 promoter polymorphisms: a genetic prognostic factor for survival in metastatic renal cell carcinoma.
    J Clin Oncol. 2007 Mar 1;25(7):845-51 PMID: 17327605
  74. Imatinib mesylate suppresses cytokine synthesis by activated CD4 T cells of patients with chronic myelogenous leukemia.
    Leukemia. 2005 Nov;19(11):1905-11 PMID: 16151467
  75. DNA alkylating therapy induces tumor regression through an HMGB1-mediated activation of innate immunity.
    J Immunol. 2011 Mar 15;186(6):3517-26 PMID: 21300822
  76. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer.
    Cancer Res. 2010 Aug 1;70(15):6171-80 PMID: 20631075
  77. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012.
    Cell Death Differ. 2012 Jan;19(1):107-20 PMID: 21760595
  78. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients.
    Clin Cancer Res. 2008 Oct 15;14(20):6674-82 PMID: 18927310
  79. Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival.
    J Clin Oncol. 2011 Apr 20;29(12):1539-46 PMID: 21422430
  80. Epidermal growth factor receptor inhibition augments the expression of MHC class I and II genes.
    Clin Cancer Res. 2011 Jul 1;17(13):4400-13 PMID: 21586626
  81. Sorafenib reduces the percentage of tumour infiltrating regulatory T cells in renal cell carcinoma patients.
    Int J Cancer. 2011 Jul 15;129(2):507-12 PMID: 20839259
  82. Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients.
    Cancer. 2006 Dec 15;107(12):2866-72 PMID: 17099880
  83. Decrease in CD4+ T-cell counts in patients with multiple myeloma treated with bortezomib.
    Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):134-7 PMID: 20371447
  84. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis.
    Pharmacol Rev. 2005 Jun;57(2):163-72 PMID: 15914465
  85. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
    Blood. 2007 Jun 15;109(12):5439-46 PMID: 17327408
  86. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy.
    Cancer Metastasis Rev. 2011 Mar;30(1):61-9 PMID: 21249425
  87. Oncogenes and tumour suppressors take on centrosomes.
    Nat Rev Cancer. 2007 Dec;7(12):911-24 PMID: 18004399
  88. Prognostic significance of macrophage infiltration in leiomyosarcomas.
    Clin Cancer Res. 2008 Mar 1;14(5):1423-30 PMID: 18316565
  89. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.
    J Pathol. 2011 Jul;224(3):389-400 PMID: 21437909
  90. Aminobisphosphonate-pretreated dendritic cells trigger successful Vgamma9Vdelta2 T cell amplification for immunotherapy in advanced cancer patients.
    Cancer Immunol Immunother. 2010 Nov;59(11):1611-9 PMID: 20582413
  91. The role of PI3K in immune cells.
    Nat Immunol. 2003 Apr;4(4):313-9 PMID: 12660731
  92. Personalized medicine in oncology: the future is now.
    Nat Rev Drug Discov. 2010 May;9(5):363-6 PMID: 20431568
  93. Molecular mechanisms of the antitumor effects of anti-CD20 antibodies.
    Front Biosci (Landmark Ed). 2011 Jan 01;16:277-306 PMID: 21196171
  94. Erlotinib hydrochloride.
    Nat Rev Drug Discov. 2005 Jan;4(1):13-4 PMID: 15690599
  95. 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. 2009 Oct;45(10):e167-74 PMID: 19576838
  96. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.
    N Engl J Med. 2002 Aug 15;347(7):481-7 PMID: 12181402
  97. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection.
    J Immunol. 2009 Nov 15;183(10):6145-50 PMID: 19841190
  98. 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. 2000 May;6(5):1875-81 PMID: 10815910
  99. Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf/ERK cascade and Akt signaling pathway.
    Toxicol Appl Pharmacol. 2011 Mar 1;251(2):130-6 PMID: 21195724
  100. The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients.
    Cancer Immunol Immunother. 2008 Aug;57(8):1115-24 PMID: 18193223
  101. Stromal gene signatures in large-B-cell lymphomas.
    N Engl J Med. 2008 Nov 27;359(22):2313-23 PMID: 19038878
  102. Immunogenic and tolerogenic cell death.
    Nat Rev Immunol. 2009 May;9(5):353-63 PMID: 19365408
  103. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment.
    Nat Rev Immunol. 2007 Jan;7(1):41-51 PMID: 17186030
  104. Cyclophosphamide induces differentiation of Th17 cells in cancer patients.
    Cancer Res. 2011 Feb 1;71(3):661-5 PMID: 21148486
  105. Improved clinical outcome in indolent B-cell lymphoma patients vaccinated with autologous tumor cells experiencing immunogenic death.
    Cancer Res. 2010 Nov 15;70(22):9062-72 PMID: 20884630
  106. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients.
    Clin Cancer Res. 2009 Mar 15;15(6):2148-57 PMID: 19276286
  107. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer.
    Cancer Immunol Immunother. 2010 May;59(5):663-74 PMID: 19890632
  108. Role of IL-1 receptor-associated kinase-M (IRAK-M) in priming of immune and inflammatory responses by nitrogen bisphosphonates.
    Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11163-8 PMID: 21690387
  109. VEGF blockade inhibits lymphocyte recruitment and ameliorates immune-mediated vascular remodeling.
    Circ Res. 2010 Aug 6;107(3):408-17 PMID: 20538685
  110. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug.
    Nat Rev Drug Discov. 2002 Jul;1(7):493-502 PMID: 12120256
  111. Oncosuppressive functions of autophagy.
    Antioxid Redox Signal. 2011 Jun;14(11):2251-69 PMID: 20712403
  112. A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients.
    J Immunother. 2010 Nov-Dec;33(9):991-8 PMID: 20948437
  113. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy.
    Cancer Immunol Immunother. 2009 Jan;58(1):49-59 PMID: 18446337
  114. Chemotherapy induces ATP release from tumor cells.
    Cell Cycle. 2009 Nov 15;8(22):3723-8 PMID: 19855167
  115. Immunogenic death of colon cancer cells treated with oxaliplatin.
    Oncogene. 2010 Jan 28;29(4):482-91 PMID: 19881547
  116. The contribution of vascular endothelial growth factor to the induction of regulatory T-cells in malignant effusions.
    Anticancer Res. 2009 Mar;29(3):881-8 PMID: 19414323
  117. 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. 2005 Nov;46(11):1581-91 PMID: 16236613
  118. Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation.
    Blood. 2008 Feb 1;111(3):1366-77 PMID: 17962511
  119. Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia.
    PLoS One. 2011 Apr 18;6(4):e18925 PMID: 21533122
  120. Gefitinib induces myeloid differentiation of acute myeloid leukemia.
    Blood. 2005 Oct 15;106(8):2841-8 PMID: 15998836
  121. Infiltration of CD14-positive macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis.
    Hepatogastroenterology. 2011 Mar-Apr;58(106):352-8 PMID: 21661395
  122. Dasatinib inhibits the secretion of TNF-alpha following TLR stimulation in vitro and in vivo.
    Exp Hematol. 2009 Dec;37(12):1435-44 PMID: 19786067
  123. Timeline: Chemotherapy and the war on cancer.
    Nat Rev Cancer. 2005 Jan;5(1):65-72 PMID: 15630416
  124. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients.
    J Exp Med. 2010 Sep 27;207(10):2175-86 PMID: 20819923
  125. Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma.
    Cancer Immunol Immunother. 2010 Jun;59(6):909-19 PMID: 20087581
  126. Factors regulating apoptosis and homeostasis of CD4+ CD25(high) FOXP3+ regulatory T cells are new therapeutic targets.
    Front Biosci. 2008 Jan 01;13:1472-99 PMID: 17981643
  127. Tumor-associated macrophages infiltration is associated with peritumoral lymphangiogenesis and poor prognosis in lung adenocarcinoma.
    Med Oncol. 2011 Dec;28(4):1447-52 PMID: 20676804
  128. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects.
    Mult Scler. 2002 Apr;8(2):142-54 PMID: 11990872
  129. Myeloid-derived suppressor cell inhibition of the IFN response in tumor-bearing mice.
    Cancer Res. 2011 Aug 1;71(15):5101-10 PMID: 21680779
  130. Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited.
    Lancet Oncol. 2007 Jan;8(1):2-3 PMID: 17196504
  131. Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells.
    Int J Cancer. 2011 Aug 15;129(4):832-8 PMID: 21710545
  132. Dasatinib inhibits the proliferation and function of CD4+CD25+ regulatory T cells.
    Br J Haematol. 2009 Jan;144(2):195-205 PMID: 19016717
  133. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome.
    J Clin Oncol. 2011 Apr 20;29(12):1612-9 PMID: 21422439
  134. Cimetidine: an anticancer drug?
    Eur J Pharm Sci. 2011 Apr 18;42(5):439-44 PMID: 21329756
  135. Telomerase peptide vaccination combined with temozolomide: a clinical trial in stage IV melanoma patients.
    Clin Cancer Res. 2011 Jul 1;17(13):4568-80 PMID: 21586625
  136. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice.
    J Clin Invest. 2011 Aug;121(8):3100-8 PMID: 21765211
  137. CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice.
    Clin Cancer Res. 2011 Apr 1;17(7):1765-75 PMID: 21233400
  138. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells.
    Clin Cancer Res. 2008 Apr 15;14(8):2413-20 PMID: 18413832
  139. Novel antifolate drugs.
    Curr Oncol Rep. 2003 Mar;5(2):114-25 PMID: 12583828
  140. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients.
    Gastroenterology. 2007 Jun;132(7):2328-39 PMID: 17570208
  141. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.
    Nat Med. 2007 Sep;13(9):1050-9 PMID: 17704786
  142. Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells.
    Cancer Lett. 2008 Dec 8;272(1):110-21 PMID: 18718708
  143. 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. 2009 Feb;37(2):256-65 PMID: 19056158
  144. OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis.
    J Exp Med. 2009 May 11;206(5):1103-16 PMID: 19414558
  145. Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer.
    Curr Opin Investig Drugs. 2010 Dec;11(12):1354-9 PMID: 21154117
  146. Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape.
    J Clin Oncol. 2010 Oct 1;28(28):4390-9 PMID: 20697078
  147. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity.
    Cancer Res. 2010 Apr 15;70(8):3052-61 PMID: 20388795
  148. Induction of TNF-alpha, uPA, IL-8 and MCP-1 by doxorubicin in human lung carcinoma cells.
    Cancer Chemother Pharmacol. 2003 Nov;52(5):391-8 PMID: 12908082
  149. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis.
    Cancer Res. 2011 Feb 1;71(3):768-78 PMID: 21156650
  150. 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. 2006 Jun 1;118(11):2790-5 PMID: 16388515
  151. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha.
    Science. 2010 Nov 5;330(6005):827-30 PMID: 21051638
  152. Monoclonal antibodies: versatile platforms for cancer immunotherapy.
    Nat Rev Immunol. 2010 May;10(5):317-27 PMID: 20414205
  153. Chemotherapy enhances vaccine-induced antitumor immunity in melanoma patients.
    Int J Cancer. 2009 Jan 1;124(1):130-9 PMID: 18839429
  154. Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice.
    J Clin Invest. 2010 Apr;120(4):1111-24 PMID: 20234093
  155. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization.
    Chem Biol. 2006 Nov;13(11):1235-42 PMID: 17114005
  156. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study.
    Blood. 2008 Feb 15;111(4):2170-80 PMID: 17925489
  157. Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer.
    J Cancer Res Clin Oncol. 2010 Oct;136(10):1585-95 PMID: 20221835
  158. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells.
    Cancer Res. 2009 Mar 15;69(6):2506-13 PMID: 19244102
  159. Drug interactions in cancer therapy.
    Nat Rev Cancer. 2006 Jul;6(7):546-58 PMID: 16794637
  160. Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome.
    N Engl J Med. 1985 Dec 5;313(23):1429-33 PMID: 3864009
  161. Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death.
    EMBO J. 2009 Mar 4;28(5):578-90 PMID: 19165151
  162. Topoisomerase inhibitors modulate expression of melanocytic antigens and enhance T cell recognition of tumor cells.
    Cancer Immunol Immunother. 2011 Jan;60(1):133-44 PMID: 21052994
  163. Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer.
    Anticancer Res. 2010 May;30(5):1807-13 PMID: 20592383
  164. Enhanced T-cell responses to glioma cells coated with the anti-EGF receptor antibody and targeted to activating FcgammaRs on human dendritic cells.
    J Immunother. 2008 Feb-Mar;31(2):113-20 PMID: 18481381
  165. 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. 2009 Sep;20(9):1548-1554 PMID: 19515749
  166. Proteasome inhibition suppresses essential immune functions of human CD4+ T cells.
    Immunology. 2008 Jun;124(2):234-46 PMID: 18217957
  167. BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs.
    Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10967-71 PMID: 20534453
  168. Multifactorial approach to predicting resistance to anthracyclines.
    J Clin Oncol. 2011 Apr 20;29(12):1578-86 PMID: 21422418
  169. Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice.
    J Clin Invest. 2010 Apr;120(4):1204-16 PMID: 20234089
  170. Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.
    BJU Int. 2011 Jun;107(12):1918-22 PMID: 21044246
  171. Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses.
    Br J Cancer. 2010 Jan 5;102(1):115-23 PMID: 19997099
  172. Cardiac side-effects of cancer chemotherapy.
    Int J Cardiol. 2010 Sep 24;144(1):3-15 PMID: 20399520
  173. Successful colon cancer eradication after chemoimmunotherapy is associated with profound phenotypic change of intratumoral myeloid cells.
    J Immunol. 2011 Jan 15;186(2):807-15 PMID: 21148040
  174. Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase.
    J Exp Med. 2010 Oct 25;207(11):2469-77 PMID: 20921286
  175. Profound inhibition of antigen-specific T-cell effector functions by dasatinib.
    Clin Cancer Res. 2008 Apr 15;14(8):2484-91 PMID: 18413841
  176. Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses.
    Blood. 2008 Jun 15;111(12):5610-20 PMID: 18310500
  177. The role of tumor stroma in the interaction between tumor and immune system.
    Curr Opin Immunol. 2005 Apr;17(2):180-6 PMID: 15766679
  178. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
    N Engl J Med. 2011 Jun 30;364(26):2517-26 PMID: 21639810
  179. How the glucocorticoids suppress immunity.
    Science. 1995 Oct 13;270(5234):232-3 PMID: 7569969
  180. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  181. Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines.
    J Immunol. 2006 Mar 1;176(5):2722-9 PMID: 16493027
  182. 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. 2007 May;56(5):641-8 PMID: 16960692
  183. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit.
    Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20410-5 PMID: 19074257
  184. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors.
    Cancer Res. 2011 Jul 15;71(14):4809-20 PMID: 21646474
  185. 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. 2011 Mar 14;208(3):469-78 PMID: 21339327
  186. Tumor cell metabolism: cancer's Achilles' heel.
    Cancer Cell. 2008 Jun;13(6):472-82 PMID: 18538731
  187. Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma.
    Int J Cancer. 2011 Jun 1;128(11):2663-72 PMID: 20715106
  188. Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer.
    Int J Cancer. 2003 Jan 1;103(1):97-100 PMID: 12455059
  189. Mitotic catastrophe: a mechanism for avoiding genomic instability.
    Nat Rev Mol Cell Biol. 2011 Jun;12(6):385-92 PMID: 21527953
  190. 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. 2002 Apr 15;62(8):2244-7 PMID: 11956077
  191. Bystander effect of vinorelbine alters antitumor immune response.
    Int J Cancer. 2011 Sep 15;129(6):1511-8 PMID: 21128224
  192. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients.
    BMC Cancer. 2010 Jun 30;10:340 PMID: 20591136
  193. Impact of interleukin-10 polymorphisms (-1082 and -3575) on the survival of patients with lymphoid neoplasms.
    Haematologica. 2007 Nov;92(11):1475-81 PMID: 18024395
  194. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study.
    J Clin Oncol. 2010 Oct 1;28(28):4324-32 PMID: 20697067
  195. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
    J Exp Med. 2010 Sep 27;207(10):2187-94 PMID: 20819927
  196. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation.
    J Exp Med. 2011 Mar 14;208(3):479-90 PMID: 21339324
  197. CD4+Foxp3+ regulatory T-cell impairment by paclitaxel is independent of toll-like receptor 4.
    Scand J Immunol. 2011 Apr;73(4):301-8 PMID: 21223350
  198. CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity.
    Prostate. 2010 Mar 1;70(4):433-42 PMID: 19866475
  199. Dasatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral and leukemia antigens.
    Exp Hematol. 2008 Oct;36(10):1297-308 PMID: 18619726
  200. Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients.
    Cancer Res. 2009 Apr 15;69(8):3563-9 PMID: 19351841
  201. IAP inhibitors enhance co-stimulation to promote tumor immunity.
    J Exp Med. 2010 Sep 27;207(10):2195-206 PMID: 20837698
  202. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant.
    J Immunol. 2008 Jul 1;181(1):776-84 PMID: 18566444
  203. Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors.
    Nat Med. 2011 Jun;17(6):700-7 PMID: 21552268
  204. 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. 2003 May 15;170(10):4905-13 PMID: 12734333
  205. Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin's lymphoma.
    Haematologica. 2011 Feb;96(2):269-76 PMID: 21071500
  206. Immune parameters affecting the efficacy of chemotherapeutic regimens.
    Nat Rev Clin Oncol. 2011 Mar;8(3):151-60 PMID: 21364688
  207. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
    N Engl J Med. 2002 Aug 15;347(7):472-80 PMID: 12181401
  208. Modulation of T-effector function by imatinib at the level of cytokine secretion.
    Exp Hematol. 2007 Aug;35(8):1266-71 PMID: 17560008
  209. An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells.
    Cancer Cell. 2011 Jan 18;19(1):101-13 PMID: 21251615
  210. Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects.
    Curr Drug Metab. 2009 Jun;10(5):470-81 PMID: 19689244
  211. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009.
    Cell Death Differ. 2009 Jan;16(1):3-11 PMID: 18846107
  212. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer.
    Nat Rev Drug Discov. 2004 May;3(5):391-400 PMID: 15136787
  213. Induction of immunogenic apoptosis by blockade of epidermal growth factor receptor activation with a specific antibody.
    J Immunol. 2011 Nov 15;187(10):4954-66 PMID: 21984704
  214. Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of melan-a-specific, tumor-reactive CTL in melanoma patients.
    Cancer Res. 2010 Sep 15;70(18):7084-92 PMID: 20823160
  215. mTOR kinase inhibitor AZD8055 enhances the immunotherapeutic activity of an agonist CD40 antibody in cancer treatment.
    Cancer Res. 2011 Jun 15;71(12):4074-84 PMID: 21540234
  216. Role of autophagy in cancer.
    Nat Rev Cancer. 2007 Dec;7(12):961-7 PMID: 17972889
  217. Oxaliplatin in combination with liver-specific expression of interleukin 12 reduces the immunosuppressive microenvironment of tumours and eradicates metastatic colorectal cancer in mice.
    Gut. 2011 Mar;60(3):341-9 PMID: 20855451
  218. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy.
    Cancer Res. 2011 Sep 1;71(17):5670-7 PMID: 21846824
  219. Identification of subtypes in human epidermal growth factor receptor 2--positive breast cancer reveals a gene signature prognostic of outcome.
    J Clin Oncol. 2010 Apr 10;28(11):1813-20 PMID: 20231686
  220. The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity.
    Int J Cancer. 2010 Nov 1;127(9):2119-28 PMID: 20143399
  221. Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer.
    Cancer Immunol Immunother. 2011 Jul;60(7):909-18 PMID: 21644034
  222. Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome.
    Cancer Immunol Immunother. 2012 Mar;61(3):353-62 PMID: 21915801
  223. Imatinib mesylate inhibits CD4+ CD25+ regulatory T cell activity and enhances active immunotherapy against BCR-ABL- tumors.
    J Immunol. 2008 Nov 15;181(10):6955-63 PMID: 18981115
  224. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation.
    Cancer Cell. 2010 Nov 16;18(5):485-98 PMID: 21035406
  225. Erlotinib antagonizes constitutive activation of SRC family kinases and mTOR in acute myeloid leukemia.
    Cell Cycle. 2011 Sep 15;10(18):3168-75 PMID: 21897118
Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1784
DOI
10.1038/nrd3626
Published
2012-02-03
Epub
2012-00-03
Pages
215-33
Language
English
Region
England
NLM ID
101124171
Subset
IM
External Links
PubMed source DOI: 10.1038/nrd3626 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2