Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy
- PMID: 28188673
- PMCID: PMC5406529
- DOI: 10.1111/cas.13194
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.
Keywords: Immune checkpoint; JAK-STAT; T cell; kinase inhibitory region; suppressors of cytokine signaling.
© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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