Cancer derives from mutant oncogenic cells, which tend to thrive within immunocompromised individuals. As the basic research on cancer goes deeper, the knowledge of the existence of a variety of antitumor components is gradually revealed. Cells including NK cells, dendritic cells, B cells and T cells, and their associated immune molecules such as cytokines, ligands and antibodies, all showed particular anti-tumor effects. At the same time, immunosuppressive cells such as regular T cells, tumor associated macrophages, regulatory DCs and myeloid derived suppressive cells, and their corresponding secretory factors were revealed to suppress anti-tumor effects. These basic research findings suggest that harnessing the immune system in the right ways might control cancer.
国家自然科学基金(31270820)
国家自然科学基金(81502679)
国家自然科学基金(81230061)
北京市科技计划(Z151100003915076)
[1] Hanahan D, Weinberg R A. Hallmarks of Cancer: The Next Generation. Cell, 2011, 144: 646-674 CrossRef PubMed Google Scholar
[2]
Muehlenbachs
A,
Bhatnagar
J,
Agudelo
C A, et al.
Malignant Transformation of
[3] Joyce J A, Fearon D T. T cell exclusion, immune privilege, and the tumor microenvironment. Science, 2015, 348: 74-80 CrossRef PubMed ADS Google Scholar
[4] Childs R W, Carlsten M. Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens. Nat Rev Drug Discov, 2015, 14: 487-498 CrossRef PubMed Google Scholar
[5] Kastenmüller W, Kastenmüller K, Kurts C, et al. Dendritic cell-targeted vaccines—hope or hype? Nat Rev Immunol, 2014, 14: 705–711. Google Scholar
[6] Germain C, Gnjatic S, Dieu-Nosjean M C. Tertiary lymphoid structure-associated b cells are key players in anti-tumor immunity. Front Immunol, 2015, 6: 67 Google Scholar
[7] Weigelin B, Bola?os E, Teijeira A, et al. Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb. Proc Natl Acad Sci USA, 2015, 112: 7551-7556 CrossRef PubMed ADS Google Scholar
[8] Haabeth O A, Tveita A A, Fauskanger M, et al. How do CD4+T cells detect and eliminate tumor cells that either lack or express MHC class Ⅱ molecules? Front Immunol, 2014, 5: 174. Google Scholar
[9] Savage P A, Malchow S, Leventhal D S. Basic principles of tumor-associated regulatory T cell biology. Trends Immunol, 2013, 34: 33-40 CrossRef PubMed Google Scholar
[10] Noy R, Pollard J W. Tumor-Associated Macrophages: From Mechanisms to Therapy. Immun, 2014, 41: 49-61 CrossRef PubMed Google Scholar
[11] Zhong H, Gutkin D W, Han B, et al. Origin and pharmacological modulation of tumor-associated regulatory dendritic cells. Int J Cancer, 2014, 134: 2633-2645 CrossRef PubMed Google Scholar
[12] Marvel D, Gabrilovich D I. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clinical Investigation, 2015, 125: 3356-3364 CrossRef PubMed Google Scholar
[13] Morton D L, Eilber F R, Holmes E C, et al. BCG lmmunotherapy of Malignant Melanoma. Ann Surgery, 1974, 180: 635-643 CrossRef Google Scholar
[14] Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature, 2011, 480: 480-489 CrossRef PubMed ADS Google Scholar
[15] Small E J, Lance R S, Gardner T A, et al. A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer. Clinical Cancer Res, 2015, 21: 3862-3869 CrossRef PubMed Google Scholar
[16] Weiner G J. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer, 2015, 15: 361-370 CrossRef PubMed Google Scholar
[17] Fan X, Quezada S A, Sepulveda M A, et al. Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy. J Exp Med, 2014, 211: 715-725 CrossRef PubMed Google Scholar
[18] Koyama S, Akbay E A, Li Y Y, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun, 2016, 7: 10501 CrossRef PubMed ADS Google Scholar
[19] Brower V. Checkpoint Blockade Immunotherapy for Cancer Comes of Age. JNCI J Natl Cancer Institute, 2015, 107: djv069-djv069 CrossRef PubMed Google Scholar
[20] Pan K, Guan X X, Li Y Q, et al. Clinical Activity of Adjuvant Cytokine-Induced Killer Cell Immunotherapy in Patients with Post-Mastectomy Triple-Negative Breast Cancer. Clinical Cancer Res, 2014, 20: 3003-3011 CrossRef PubMed Google Scholar
[21] Rosenberg S A, Restifo N P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science, 2015, 348: 62-68 CrossRef PubMed ADS Google Scholar
[22] Stevanovi S, Draper L M, Langhan M M, et al. Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus-Targeted Tumor-Infiltrating T Cells. J Clinical Oncology, 2015, 33: 1543-1550 CrossRef PubMed Google Scholar
[23] Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity.. Proc Natl Acad Sci, 1989, 86: 10024-10028 CrossRef Google Scholar
[24] Porter D L, Hwang W T, Frey N V, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Translational Med, 2015, 7: 303ra139-303ra139 CrossRef PubMed Google Scholar
[25] Lee D W, Kochenderfer J N, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet, 2015, 385: 517-528 CrossRef Google Scholar
[26] Dai H, Zhang W, Li X, et al. Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. OncoImmunol, 2015, 4: e1027469 CrossRef PubMed Google Scholar
[27] Kochenderfer J N, Dudley M E, Kassim S H, et al. Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor. J Clinical Oncology, 2015, 33: 540-549 CrossRef PubMed Google Scholar
[28] Wang Q S, Wang Y, Lv H Y, et al. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther, 2015, 23: 184-191 Google Scholar
[29] Garfall A L, Maus M V, Hwang W T, et al. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. N Engl J Med, 2015, 373: 1040-1047 CrossRef PubMed Google Scholar
[30] Dai H, Wang Y, Lu X, et al. Chimeric antigen receptors modified T-Cells for cancer therapy. J Natl Cancer Inst, 2016, doi: 10.1093/jnci/djv439. Google Scholar
[31] Clay T M, Custer M C, Sachs J, et al. Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol, 1999, 163: 507-513 Google Scholar
[32] Kershaw M H, Westwood J A, Slaney C Y, et al. Clinical application of genetically modified T cells in cancer therapy. Clin Trans Immunol, 2014, 3: e16 CrossRef PubMed Google Scholar
[33] Robbins P F, Kassim S H, Tran T L N, et al. A Pilot Trial Using Lymphocytes Genetically Engineered with an NY-ESO-1-Reactive T-cell Receptor: Long-term Follow-up and Correlates with Response. Clinical Cancer Res, 2015, 21: 1019-1027 CrossRef PubMed Google Scholar
[34] Rapoport A P, Stadtmauer E A, Binder-Scholl G K, et al. NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med, 2015, 21: 914-921 CrossRef PubMed Google Scholar
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