Journal
CANCER CELL
Volume 36, Issue 6, Pages 597-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.10.008
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Funding
- BMS Foundation
- Janssen Horizon Foundation
- Societe Francaise des Cancers de l'Enfant (SFCE)
- association Enfants et Sante
- association L'Etoile de Martin
- Abigael association
- ADAM association
- Au Nom d'Andrea association
- Marabout de Ficelles association
- SiRIC-Curie Program [INCaDGOS-4654, INCaDGOS-12554]
- Institut National de la Sante et de la Recherche Medicale
- Curie Institute
- Ligue Nationale Contre Le Cancer
- LabEx DCBIOL [ANR-10-IDEX-0001-02 PSL, ANR-11-LABX-0043]
- Center of Clinical Investigation [CIC IGR-Curie 1428]
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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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