Reduced infiltration of anti-tumor lymphocytes remains a major cause of tumor immune evasion and is correlated with poor cancer survival. Here, we found that upregulation of regulator of G protein signaling (RGS)1 in helper T_H1 cells and cytotoxic T lymphocytes (CTLs) reduced their trafficking to and survival in tumors and was associated with shorter survival of patients with breast and lung cancer. RGS1 was upregulated by type II interferon (IFN)–signal transducer and activator of transcription (STAT)1 signaling and impaired trafficking of circulating T cells to tumors by inhibiting calcium influx and suppressing activation of the kinases ERK and AKT. RGS1 knockdown in adoptively transferred tumor-specific CTLs significantly increased their infiltration and survival in breast and lung tumor grafts and effectively inhibited tumor growth in vivo, which was further improved when combined with programmed death ligand (PD-L)1 checkpoint inhibition. Our findings reveal RGS1 is important for tumor immune evasion and suggest that targeting RGS1 may provide a new strategy for tumor immunotherapy.

抗肿瘤淋巴细胞浸润减少仍然是肿瘤免疫逃避的主要原因，并且与癌症存活率低相关。在这里，我们发现辅助性 T _H 1 细胞和细胞毒性 T 淋巴细胞 (CTL) 中 G 蛋白信号传导调节因子 (RGS)1 的上调会减少它们向肿瘤的运输和在肿瘤中的存活，并与乳腺癌和肺癌患者的较短存活期相关。 RGS1 被 II 型干扰素 (IFN)——信号转导器和转录激活剂 (STAT)1 信号传导上调，并通过抑制钙流入和抑制激酶 ERK 和 AKT 的激活来损害循环 T 细胞向肿瘤的运输。过继转移的肿瘤特异性CTL中的RGS1敲低显着增加了它们在乳腺和肺肿瘤移植物中的浸润和存活，并有效抑制了体内肿瘤的生长，当与程序性死亡配体（PD-L）1检查点抑制相结合时，这种效果进一步得到改善。我们的研究结果揭示了 RGS1 对于肿瘤免疫逃避很重要，并表明靶向 RGS1 可能为肿瘤免疫治疗提供新策略。