SOCS1, also known as STAT-induced STAT inhibitor (SSI) or JAK-binding protein (JAB), is a member of the SOCS family. It functions as a negative regulator of cytokine signaling, participating in cell signaling and ubiquitination-mediated protein degradation processes. These functions are crucial for cell growth, proliferation, and immune homeostasis, with a key role in the regulation of IFN-γ, IL-12, and IL-2 family cytokines signaling pathways [1,2].

In CD4+ T cells, SOCS1 acts as a major non-redundant checkpoint, integrating IL-2 and IFN-γ signals to block downstream pathways and limit CD4+ T helper 1 (TH1) cell response. Inactivation of SOCS1 in murine and human CD4+ T cell antitumor adoptive therapies restored intratumor accumulation, proliferation/survival, persistence, and polyfunctionality, promoting tumor rejection [3]. In CD8+ T cells, SOCS1 deletion improved survival and effector functions [3]. In the thymus, SOCS1-deficient mice show that SOCS1 prevents thymocytes failing positive selection from surviving and expanding, ensures negative selection, and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, it controls T cell stimulatory cytokine production, attenuates CD8+ T cell sensitivity to cytokine stimulation and antigen-non-specific activation, and contributes to peripheral T cell tolerance [4]. In addition, SOCS1-deficient mouse models demonstrate its critical role in maintaining the stability of T regulatory cells and preventing their transformation into pathogenic Th17 and Th1 cells [4]. Loss of SOCS1 in the mouse liver increases the rate of liver regeneration and renders hepatocytes more susceptible to neoplastic transformation [5].

In conclusion, SOCS1 is a critical regulator in immune homeostasis, inflammation, and tumor immunity. Through gene knockout mouse models, its role in T cell regulation, immune tolerance, and cancer has been revealed. Understanding SOCS1's functions helps in developing new strategies for treating autoimmune diseases and cancer, such as optimizing adoptive immunotherapy and immune checkpoint blockade [2,3,4].