Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors

Cancer Cell. 2019 Dec 9;36(6):597-612.e8. doi: 10.1016/j.ccell.2019.10.008. Epub 2019 Nov 7.


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.

Keywords: AT/RT; SMARCB1; SWI/SNF; T cell receptor; endogenous retrovirus; immunotherapy; pediatric cancer; rhabdoid tumor; single-cell RNA sequencing; tumor immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly / immunology*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Humans
  • Immunohistochemistry / methods
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Rhabdoid Tumor / genetics*
  • Rhabdoid Tumor / immunology*
  • T-Lymphocytes / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors