Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer
Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer
复制标题
靶向肿瘤特异性 T 细胞中 G 蛋白信号传导 1 的调节因子可增强其向乳腺癌的运输
DOI：
10.1038/s41590-021-00939-9
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发表时间：
2021-06-17
影响因子：
30.5
通讯作者：
Song, Erwei
中科院分区：
文献类型：
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作者：
Huang, Di;Chen, Xueman;Song, Erwei
抗肿瘤淋巴细胞浸润的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TH 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的上调减少了它们在肿瘤中的运输和存活，并与乳腺癌和肺癌患者的生存期缩短相关。RGS 1通过II型干扰素（IFN）-信号转导子和转录激活子（STAT）1信号转导上调，并通过抑制钙内流和抑制激酶ERK和AKT的活化，削弱循环T细胞向肿瘤的运输。过继转移的肿瘤特异性CTL中的RGS 1敲低显著增加了它们在乳腺和肺肿瘤移植物中的浸润和存活，并有效抑制体内肿瘤生长，当与程序性死亡配体（PD-L）1检查点抑制结合时，其进一步改善。我们的研究结果揭示了RGS 1在肿瘤免疫逃避中的重要作用，并表明靶向RGS 1可能为肿瘤免疫治疗提供新的策略。
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 TH1 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.RGS1knockdown 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.