当前位置:科学网首页 > 小柯机器人 >详情
肿瘤中RNA结合蛋白FMRP的异常过度表达介导免疫逃逸
作者:小柯机器人 发布时间:2022/11/20 20:35:19

瑞士洛桑联邦理工学院Douglas Hanahan小组发现,肿瘤中RNA结合蛋白FMRP的异常过度表达介导免疫逃逸。相关论文于2022年11月18日发表在《科学》杂志上。

研究人员确定了免疫逃逸的一个组成部分,涉及固体肿瘤中脆弱X型智力迟钝蛋白(FMRP)的频繁上调。FMRP抑制了免疫攻击,这一点被缺乏其表达的癌症细胞所证实。FMRP缺陷的肿瘤被激活的T细胞浸润,损害了肿瘤的生长,并提高了小鼠的生存率。

从机制上讲,FMRP的免疫抑制是多因素的,涉及抑制化学吸引剂C-C图案趋化因子配体7(CCL7),同时上调三种免疫调节剂-白介素-33(IL-33)、肿瘤分泌蛋白S(PROS1)和细胞外囊泡。基因特征将FMRP的癌症网络与癌症患者的不良预后和对治疗的反应联系起来。总的来说,FMRP被认为是协调抗肿瘤免疫反应多方面障碍的一个调节器。

据悉,许多人类癌症表现出逃逸适应性免疫系统攻击的能力。

附:英文原文

Title: Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion

Author: Qiqun Zeng, Sadegh Saghafinia, Agnieszka Chryplewicz, Nadine Fournier, Lucine Christe, Yu-Qing Xie, Jeremy Guillot, Simge Yucel, Pumin Li, José A. Galván, Eva Karamitopoulou, Inti Zlobec, Dalya Ataca, Fleuriane Gallean, Peng Zhang, José Antonio Rodriguez-Calero, Mark Rubin, Mélanie Tichet, Krisztian Homicsko, Douglas Hanahan

Issue&Volume: 2022-11-18

Abstract: Many human cancers manifest the capability to circumvent attack by the adaptive immune system. In this work, we identified a component of immune evasion that involves frequent up-regulation of fragile X mental retardation protein (FMRP) in solid tumors. FMRP represses immune attack, as revealed by cancer cells engineered to lack its expression. FMRP-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, FMRP’s immunosuppression was multifactorial, involving repression of the chemoattractant C-C motif chemokine ligand 7 (CCL7) concomitant with up-regulation of three immunomodulators—interleukin-33 (IL-33), tumor-secreted protein S (PROS1), and extracellular vesicles. Gene signatures associate FMRP’s cancer network with poor prognosis and response to therapy in cancer patients. Collectively, FMRP is implicated as a regulator that orchestrates a multifaceted barrier to antitumor immune responses.

DOI: abl7207

Source: https://www.science.org/doi/10.1126/science.abl7207

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037