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