title: Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy.
abstract: Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine interferon-γ (IFNγ) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway. Among SOCS proteins, CIS, SOCS1, and SOCS3 proteins can be considered the third immunocheckpoint molecules since they regulate cytokine signals that control the polarization of CD4+T cells and the maturation of CD8+T cells. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in terms of their anti-tumor immunity and potential applications.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Chikuma
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kanamori
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Setsuko
authors.initials: S
authors.lastname: Mise-Omata
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Akihiko
authors.identifier: http://orcid.org/0000-0001-5676-8949
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000276:immunology* / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000276:immunology* / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Immune checkpoint; JAK-STAT; T cell; kinase inhibitory region; suppressors of cytokine signaling