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科学家发现增强肿瘤特异性T细胞在乳腺癌中浸润的通路
2021-06-20 21:16

中山大学宋尔卫、苏士成等研究人员合作发现增强肿瘤特异性T细胞在乳腺癌中浸润的通路。相关论文于2021年6月17日在线发表在《自然—免疫学》杂志上。

研究人员发现,辅助TH1细胞和细胞毒性T淋巴细胞(CTL)中RGS1(regulator of G protein signaling 1)的上调减少了它们向肿瘤的运输和存活,并且与乳腺癌和肺癌患者的存活期缩短有关。RGS1被II型干扰素(IFN)-STAT1(signal transducer and activator of transcription 1)信号上调,并通过抑制钙内流以及抑制激酶ERK和AKT的激活来削弱循环T细胞向肿瘤的运输。

过继转移的肿瘤特异性CTL中的RGS1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,并有效地抑制了体内肿瘤生长,当与程序性死亡配体1(PD-L1)检查点抑制结合时,这一点得到进一步改善。这些研究结果表明RGS1对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的策略。

据介绍,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。

附:英文原文

Title: Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer

Author: Di Huang, Xueman Chen, Xin Zeng, Liyan Lao, Jiaqian Li, Yue Xing, Yiwen Lu, Qian Ouyang, Jianing Chen, Linbin Yang, Fengxi Su, Herui Yao, Qiang Liu, Shicheng Su, Erwei Song

Issue&Volume: 2021-06-17

Abstract: 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. 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.

DOI: 10.1038/s41590-021-00939-9

Source: https://www.nature.com/articles/s41590-021-00939-9

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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