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Publication : Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors.

First Author  Leruste A Year  2019
Journal  Cancer Cell Volume  36
Issue  6 Pages  597-612.e8
PubMed ID  31708437 Mgi Jnum  J:282671
Mgi Id  MGI:6381550 Doi  10.1016/j.ccell.2019.10.008
Citation  Leruste A, et al. (2019) Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors. Cancer Cell 36(6):597-612.e8
abstractText  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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