| Literature DB >> 31708437 |
Amaury Leruste1, Jimena Tosello2, Rodrigo Nalio Ramos2, Arnault Tauziède-Espariat3, Solène Brohard4, Zhi-Yan Han1, Kevin Beccaria5, Mamy Andrianteranagna6, Pamela Caudana2, Jovan Nikolic7, Céline Chauvin1, Leticia Laura Niborski2, Valeria Manriquez2, Wilfrid Richer2, Julien Masliah-Planchon8, Sandrine Grossetête-Lalami9, Mylene Bohec10, Sonia Lameiras10, Sylvain Baulande10, Celio Pouponnot11, Aurore Coulomb12, Louise Galmiche13, Didier Surdez9, Nicolas Servant6, Julie Helft2, Christine Sedlik2, Stéphanie Puget5, Philippe Benaroch7, Olivier Delattre9, Joshua J Waterfall14, Eliane Piaggio15, Franck Bourdeaut16.
Abstract
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.Entities:
Keywords: AT/RT; SMARCB1; SWI/SNF; T cell receptor; endogenous retrovirus; immunotherapy; pediatric cancer; rhabdoid tumor; single-cell RNA sequencing; tumor immunology
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Year: 2019 PMID： 31708437 DOI： 10.1016/j.ccell.2019.10.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743