PDF(Pubmed)
Abstract：
The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators of cytokine signaling. SOCS1 is the prototypical member of the SOCS family and functions in a classic negative-feedback loop to inhibit signaling in response to interferon, interleukin-12 and interleukin-2 family cytokines. These cytokines have a critical role in orchestrating our immune defence against viral pathogens and cancer. The ability of SOCS1 to limit cytokine signaling positions it as an important immune checkpoint, as evidenced by the detection of detrimental SOCS1 variants in patients with cytokine-driven inflammatory and autoimmune disease. SOCS1 has also emerged as a key checkpoint that restricts anti-tumor immunity, playing both a tumor intrinsic role and impacting the ability of various immune cells to mount an effective anti-tumor response. In this review, we describe the mechanism of SOCS1 action, focusing on the role of SOCS1 in autoimmunity and cancer, and discuss the potential for new SOCS1-directed cancer therapies that could be used to enhance adoptive immunotherapy and immune checkpoint blockade.
摘要：
细胞因子信号传导抑制蛋白(SOCS)家族蛋白是细胞因子信号传导的重要负调节因子。SOCS1是SOCS家族的典型成员，在经典的负反馈回路中发挥作用，以抑制响应干扰素的信号传导。白细胞介素-12和白细胞介素-2家族细胞因子。这些细胞因子在协调我们对病毒病原体和癌症的免疫防御中具有关键作用。SOCS1限制细胞因子信号传导的能力将其定位为重要的免疫检查点，在细胞因子驱动的炎症和自身免疫性疾病患者中检测到有害的SOCS1变体证明了这一点。SOCS1也已成为限制抗肿瘤免疫的关键检查点，发挥肿瘤内在作用，并影响各种免疫细胞建立有效抗肿瘤反应的能力。在这次审查中,我们描述了SOCS1作用的机制，关注SOCS1在自身免疫和癌症中的作用，并讨论了SOCS1靶向癌症新疗法的潜力，这些疗法可用于增强过继免疫疗法和免疫检查点阻断。
