Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors

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.
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Submitted on : Friday, November 8, 2019 - 10:23:25 AM
Last modification on : Thursday, November 14, 2019 - 1:24:04 AM



Amaury Leruste, Jimena Tosello, Rodrigo Nalio Ramos, Arnault Tauziède-Espariat, Solène Brohard, et al.. Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors. Cancer Cell, Elsevier, 2019, ⟨10.1016/j.ccell.2019.10.008⟩. ⟨hal-02355172⟩



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