title: Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation.
abstract: Although recent cancer immunotherapy strategies, including immune-checkpoint blockade (i.e. blocking PD-1, PD-L1 or CTLA-4), have shown durable clinical effects in some (but not all) patients with various advanced cancers, further understanding of human immunopathology, particularly in tumor microenvironments, is essential to improve this type of therapy. The major hurdle for immunotherapy is the immunosuppression that is found in cancer patients. There are two types of immunosuppression: one is induced by gene alterations in cancer; the other is local adaptive immunosuppression, triggered by tumor-specific T cells in tumors. The former is caused by multiple mechanisms via various immunosuppressive molecules and via cells triggered by gene alterations, including activated oncogenes, in cancer cells. The various immunosuppressive mechanisms involve signaling cascades that vary among cancer types, subsets within cancer types and individual cancers. Therefore, personalized immune-interventions are necessary to appropriately target oncogene-induced signaling that modulates anti-cancer immune responses, on the basis of genetic and immunological analysis of each patient. Further understanding of human cancer immunopathology may lead to real improvement of current cancer immunotherapies.
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yaguchi
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan yutakawa@keio.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D057285:Precision Medicine; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D061025:Costimulatory and Inhibitory T-Cell Receptors; D011948:Receptors, Antigen, T-Cell
keywords: cancer immunotherapy; immune-checkpoint; immunosuppression; oncogene