Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy

Inhibition of immune checkpoint molecules, PD ‐1 and CTLA 4, has been shown to be a promising cancer treatment. PD ‐1 and CTLA 4 inhibit TCR and co‐stimulatory signals. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine interferon‐γ ( IFN γ) plays an important role in anti‐tumor immunity by activating cytotoxic T cells ( CTL s). 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 , SOCS 1, and SOCS 3 proteins can be considered the third immunocheckpoint molecules since they regulate cytokine signals that control the polarization of CD 4 + T cells and the maturation of CD 8 + T cells. This review summarizes recent progress on CIS , SOCS 1, and SOCS 3 in terms of their anti‐tumor immunity and potential applications.