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Stimulating immune responses to fight cancer: Basic biology and mechanisms
Author(s) -
O'Byrne Kenneth
Publication year - 2015
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12410
Subject(s) - immune system , melanoma , immunotherapy , cancer , cancer research , immunology , cancer immunotherapy , cytotoxic t cell , inflammation , immune checkpoint , biology , lung cancer , antigen , cancer cell , medicine , in vitro , biochemistry , genetics
Chronic inflammation is now recognized as a major cause of malignant disease. In concert with various mechanisms (including DNA instability), hypoxia and activation of inflammatory bioactive lipid pathways and pro‐inflammatory cytokines open the doorway to malignant transformation and proliferation, angiogenesis, and metastasis in many cancers. A balance between stimulatory and inhibitory signals regulates the immune response to cancer. These include inhibitory checkpoints that modulate the extent and duration of the immune response and may be activated by tumor cells. This contributes to immune resistance, especially against tumor antigen‐specific T ‐cells. Targeting these checkpoints is an evolving approach to cancer immunotherapy, designed to foster an immune response. The current focus of these trials is on the programmed cell death protein 1 ( PD ‐1) receptor and its ligands ( PD ‐ L 1, PD ‐ L 2) and cytotoxic T ‐lymphocyte‐associated protein 4 ( CTLA ‐4). Researchers have developed anti‐ PD ‐1 and anti‐ PDL ‐1 antibodies that interfere with the ligands and receptor and allow the tumor cell to be recognized and attacked by tumor‐infiltrating T ‐cells. These are currently being studied in lung cancer. Likewise, CTLA ‐4 inhibitors, which have had success treating advanced melanoma, are being studied in lung cancer with encouraging results.