title: Roles of regulatory T cells in cancer immunity.
abstract: CD4(+) regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decreased ratios of CD8(+) T cells to Tregs among tumor-infiltrating lymphocytes are correlated with poor prognosis in various types of human cancers. The recent success of cancer immunotherapy represented by immune checkpoint blockade has provided a new insight in cancer treatment, yet more than half of the treated patients did not experience clinical benefits. Identifying biomarkers that predict clinical responses and developing novel immunotherapies are therefore urgently required. Cancer patients whose tumors contain a large number of neoantigens stemming from gene mutations, which have not been previously recognized by the immune system, provoke strong antitumor T-cell responses associated with clinical responses following immune checkpoint blockade, depending on the resistance to Treg-mediated suppression. Thus, integration of a strategy restricting Treg-mediated immune suppression may expand the therapeutic spectrum of cancer immunotherapy towards patients with a lower number of neoantigens. In this review, we address the current understanding of Treg-mediated immune suppressive mechanisms in cancer, the involvement of Tregs in cancer immunotherapy, and strategies for effective and tolerable Treg-targeted therapy.
authors.affiliation: Division of Cancer Immunology, EPOC, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan and.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Division of Cancer Immunology, EPOC, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan and Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan hnishika@east.ncc.go.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
mesh_terms: D016827:CD8 Antigens / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019139:Tumor Escape
chemical_list: D016827:CD8 Antigens; D019496:Cancer Vaccines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Treg-targeted therapy; immune checkpoint inhibitors; immune suppression