Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors.,Cancer Cell

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Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors.
Cancer Cell ( IF 48.8 ) Pub Date : 2019-11-07 , DOI: 10.1016/j.ccell.2019.10.008
Amaury Leruste ₁ , Jimena Tosello ₂ , Rodrigo Nalio Ramos ₂ , Arnault Tauziède-Espariat ₃ , Solène Brohard ₄ , Zhi-Yan Han ₁ , Kevin Beccaria ₅ , Mamy Andrianteranagna ₆ , Pamela Caudana ₂ , Jovan Nikolic ₇ , Céline Chauvin ₁ , Leticia Laura Niborski ₂ , Valeria Manriquez ₂ , Wilfrid Richer ₂ , Julien Masliah-Planchon ₈ , Sandrine Grossetête-Lalami ₉ , Mylene Bohec ₁₀ , Sonia Lameiras ₁₀ , Sylvain Baulande ₁₀ , Celio Pouponnot ₁₁ , Aurore Coulomb ₁₂ , Louise Galmiche ₁₃ , Didier Surdez ₉ , Nicolas Servant ₆ , Julie Helft ₂ , Christine Sedlik ₂ , Stéphanie Puget ₅ , Philippe Benaroch ₇ , Olivier Delattre ₉ , Joshua J Waterfall ₁₄ , Eliane Piaggio ₂ , Franck Bourdeaut ₁

Affiliation

PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
Sainte-Anne Hospital, Department of Neuropathology, Paris, France.
PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
AP-HP, Necker Hospital, Department of Neurosurgery, Paris, France.
PSL Research University, Institut Curie Research Center, INSERM U900, Paris, France; MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France.
PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
PSL Research University, Institut Curie Hospital, Laboratory of Somatic Genetics, Paris, France.
PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France.
PSL Research University, Institut Curie Research Center, CNRS UMR 3347, INSERM U1021, Orsay, France.
AP-HP, Armand Trousseau Hospital, Department of Pathology, Paris, France.
AP-HP, Necker Hospital, Department of Pathology, Paris, France.
PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France.

Rhabdoid tumors (RTs) are genomically simple pediatric cancers driven by the biallelic inactivation of SMARCB1, leading to SWI/SNF chromatin remodeler complex deficiency. Comprehensive evaluation of the immune infiltrates of human and mice RTs, including immunohistochemistry, bulk RNA sequencing and DNA methylation profiling studies showed a high rate of tumors infiltrated by T and myeloid cells. Single-cell RNA (scRNA) and T cell receptor sequencing highlighted the heterogeneity of these cells and revealed therapeutically targetable exhausted effector and clonally expanded tissue resident memory CD8+ T subpopulations, likely representing tumor-specific cells. Checkpoint blockade therapy in an experimental RT model induced the regression of established tumors and durable immune responses. Finally, we show that one mechanism mediating RTs immunogenicity involves SMARCB1-dependent re-expression of endogenous retroviruses and interferon-signaling activation.

中文翻译：

克隆扩增的T细胞揭示了横纹肌瘤的免疫原性。

横纹肌瘤（RTs）是基因组简单的儿科癌症，由SMARCB1的双等位基因失活驱动，导致SWI / SNF染色质重塑剂复合物缺乏。对人和小鼠RTs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精疲力竭效应子和克隆扩展的组织驻留记忆CD8 + T亚群，可能代表了肿瘤特异性细胞。实验性RT模型中的检查点封锁疗法可诱导已建立的肿瘤消退并产生持久的免疫反应。最后，

更新日期：2019-11-09

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