title: Melanoma Cells Control Antimelanoma CTL Responses via Interaction between TIGIT and CD155 in the Effector Phase.
abstract: Recently, T-cell immunoreceptor with Ig and ITIM domains (TIGIT) was reported as a candidate for novel immune checkpoints. However, the impact of TIGIT on melanoma-specific cytotoxic T lymphocytes in the effector phase remains unclear. In this study, we demonstrated that melanoma cells control antimelanoma cytotoxic T lymphocyte responses via the TIGIT-CD155 interaction in the effector phase. TIGIT is an inhibitory receptor expressed on T cells, and CD155 is one of the cognate ligands expressed on the tumor cells or antigen-presenting cells. First, we confirmed that CD155 was constitutively expressed on melanoma cells. We then demonstrated that CD155 on melanoma cells suppressed cytokine release from melanoma-specific cytotoxic T lymphocytes via interaction with TIGIT. Overexpression of CD155 enhanced and its downregulation attenuated the suppressive effect. This suggested that antimelanoma cytotoxic T lymphocyte responses are controlled not only by an imbalance in CD226 (an activating molecule that binds to CD155) and TIGIT expression on T cells but also by the expression levels of CD155 on melanoma cells. In addition, the co-blockade of TIGIT and PD-1 signals synergistically elicited a response of tumor-infiltrating lymphocytes on autologous melanoma cells. These results suggest that the CD155-TIGIT interaction should be blocked for enhancement of antimelanoma immune responses.
authors.affiliation: Department of Dermatology, University of Yamanashi, Shimokato, Chuo, Yamanashi, Japan. Electronic address: tinozume@yamanashi.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inozume
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yaguchi
authors.affiliation: Department of Dermatology, University of Yamanashi, Shimokato, Chuo, Yamanashi, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Furuta
authors.affiliation: Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Dermatology, University of Yamanashi, Shimokato, Chuo, Yamanashi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimada
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; C510162:CTAG2 protein, human; D016207:Cytokines; D027701:Organic Cation Transport Proteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D011991:Receptors, Virus; C510732:SLC44A1 protein, human; C534712:TIGIT protein, human; C066100:poliovirus receptor