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信号转导子和转录激活子 3 信号在肿瘤免疫逃逸中的作用。

Signal transducer and activator of transcription 3 signaling in tumor immune evasion.

机构信息

College of Life Science, Yangtze University, Jingzhou 434025, China.

Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Králové 500 03, Czech Republic.

出版信息

Pharmacol Ther. 2022 Feb;230:107969. doi: 10.1016/j.pharmthera.2021.107969. Epub 2021 Aug 24.

Abstract

The underlying mechanism of tumor immune evasion is a highly concerning subject for researchers. Increasing evidences reveal that the over-activated signal transducer and activator of transcription 3 (STAT3) is a crucial molecular hub in malignant tumors. STAT3 controls autophagy molecules that impair CTL-mediated tumor cell lysis, inhibiting natural killer cells and inducing apoptosis in T lymphocytes to create an immunosuppressive environment. STAT3 signaling regulates the expression of immune factors and recruits immunosuppressive cells to establish a tolerant tumor microenvironment (TME). STAT3 signaling regulates the expression of immune factors and recruits immunosuppressive cells to create an immunosuppressive environment. All this aid tumor cells in escaping from immune surveillance. In this review, we outlined the STAT3-mediated mechanisms involved in tumor immune evasion and their potential regulatory functions in the TME. We discussed the impact of STAT3 signaling on PD-L1, HIF-1α, exosome, lncRNA, and autophagy in the promotion of tumor immune evasion and highlighted the recent research on STAT3 signaling and tumor immune evasion that may assist in developing effective STAT3-targeted drugs for advancing immunotherapy.

摘要

肿瘤免疫逃逸的潜在机制是研究人员高度关注的课题。越来越多的证据表明,过度激活的信号转导和转录激活因子 3(STAT3)是恶性肿瘤中的关键分子枢纽。STAT3 控制自噬分子,损害 CTL 介导的肿瘤细胞裂解,抑制自然杀伤细胞并诱导 T 淋巴细胞凋亡,从而形成免疫抑制环境。STAT3 信号通路调节免疫因子的表达并招募免疫抑制细胞,以建立耐受的肿瘤微环境(TME)。STAT3 信号通路调节免疫因子的表达并招募免疫抑制细胞,以建立免疫抑制环境。所有这些都有助于肿瘤细胞逃避免疫监视。在这篇综述中,我们概述了 STAT3 介导的肿瘤免疫逃逸机制及其在 TME 中的潜在调节功能。我们讨论了 STAT3 信号对 PD-L1、HIF-1α、外泌体、lncRNA 和自噬在促进肿瘤免疫逃逸中的作用,并强调了 STAT3 信号与肿瘤免疫逃逸的最新研究,这可能有助于开发有效的 STAT3 靶向药物,以推进免疫治疗。

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