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研究揭示横纹肌样瘤免疫原性
作者:小柯机器人 发布时间:2019/11/8 13:18:37

法国巴黎文理研究型大学Franck Bourdeaut、Eliane Piaggio以及Joshua J. Waterfall等研究人员合作揭示了横纹肌样瘤(RT)的免疫原性。相关论文2019年11月7日在线发表于《癌细胞》。

研究人员对人和小鼠RT的免疫浸润液的综合评估,包括免疫组织化学、大量RNA测序和DNA甲基化谱分析研究表明,T和髓样细胞浸润的肿瘤发生率很高。单细胞RNA(scRNA)和T细胞受体测序突显了这些细胞的异质性,并揭示了可治疗靶向的耗竭效应细胞和克隆扩展的组织驻留记忆CD8阳性T亚群,这可能代表了肿瘤特异性细胞。实验性RT模型中的检查点抑制疗法可诱导已建立肿瘤的消退和持久的免疫反应。最后,研究人员表明介导RT免疫原性的机制涉及了依赖SMARCB1内源性逆转录病毒的重新表达和干扰素信号激活。

据介绍,RT是基因组简单的儿科癌症,由SMARCB1的双等位基因失活驱动,从而导致SWI/SNF染色质重塑复合物缺乏。

附:英文原文

Title: Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors

Author: Amaury Leruste, Jimena Tosello, Rodrigo Nalio Ramos, Arnault Tauziède-Espariat, Solène Brohard, Zhi-Yan Han, Kevin Beccaria, Mamy Andrianteranagna, Pamela Caudana, Jovan Nikolic, Céline Chauvin, Leticia Laura Niborski, Valeria Manriquez, Wilfrid Richer, Julien Masliah-Planchon, Sandrine Grossetête-Lalami, Mylene Bohec, Sonia Lameiras, Sylvain Baulande, Celio Pouponnot, Aurore Coulomb, Louise Galmiche, Didier Surdez, Nicolas Servant, Julie Helft, Christine Sedlik, Stéphanie Puget, Philippe Benaroch, Olivier Delattre, Joshua J. Waterfall, Eliane Piaggio, Franck Bourdeaut

Issue&Volume: November 07, 2019

Abstract: Rhabdoid tumors (RTs) are genomically simple pediatric cancers driven by the biallelicinactivation of SMARCB1, leading to SWI/SNF chromatin remodeler complex deficiency. Comprehensive evaluationof the immune infiltrates of human and mice RTs, including immunohistochemistry, bulkRNA sequencing and DNA methylation profiling studies showed a high rate of tumorsinfiltrated by T and myeloid cells. Single-cell RNA (scRNA) and T cell receptor sequencinghighlighted the heterogeneity of these cells and revealed therapeutically targetableexhausted effector and clonally expanded tissue resident memory CD8+ T subpopulations, likely representing tumor-specific cells. Checkpoint blockade therapyin an experimental RT model induced the regression of established tumors and durableimmune responses. Finally, we show that one mechanism mediating RTs immunogenicityinvolves SMARCB1-dependent re-expression of endogenous retroviruses and interferon-signalingactivation.

DOI: 10.1016/j.ccell.2019.10.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30482-9

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx