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Cancer cell
12 09, 2019;36 (6): 597-612.e8.

Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors.

Amaury Leruste, Jimena Tosello, Rodrigo Nalio Ramos, Arnault Tauziède-Espariat, Solène Brohard, Zhi-Yan Han, Kevin Beccaria, Mamy Andrianteranagna, Pamela Caudana, Jovan Nikolic, Céline Chauvin, Leticia Laura Niborski, Valeria Manriquez, Wilfrid Richer, Julien Masliah-Planchon, Sandrine Grossetête-Lalami, Mylene Bohec, Sonia Lameiras, Sylvain Baulande, Celio Pouponnot, Aurore Coulomb, Louise Galmiche, Didier Surdez, Nicolas Servant, Julie Helft, Christine Sedlik, Stéphanie Puget, Philippe Benaroch, Olivier Delattre, Joshua J Waterfall, Eliane Piaggio, Franck Bourdeaut
Author Information
  1. Amaury Leruste: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  2. Jimena Tosello: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  3. Rodrigo Nalio Ramos: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  4. Arnault Tauziède-Espariat: Sainte-Anne Hospital, Department of Neuropathology, Paris, France.
  5. Solène Brohard: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  6. Zhi-Yan Han: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  7. Kevin Beccaria: AP-HP, Necker Hospital, Department of Neurosurgery, Paris, France.
  8. Mamy Andrianteranagna: PSL Research University, Institut Curie Research Center, INSERM U900, Paris, France; MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France.
  9. Pamela Caudana: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  10. Jovan Nikolic: PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  11. Céline Chauvin: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  12. Leticia Laura Niborski: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  13. Valeria Manriquez: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  14. Wilfrid Richer: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  15. Julien Masliah-Planchon: PSL Research University, Institut Curie Hospital, Laboratory of Somatic Genetics, Paris, France.
  16. Sandrine Grossetête-Lalami: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  17. Mylene Bohec: PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France.
  18. Sonia Lameiras: PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France.
  19. Sylvain Baulande: PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France.
  20. Celio Pouponnot: PSL Research University, Institut Curie Research Center, CNRS UMR 3347, INSERM U1021, Orsay, France.
  21. Aurore Coulomb: AP-HP, Armand Trousseau Hospital, Department of Pathology, Paris, France.
  22. Louise Galmiche: AP-HP, Necker Hospital, Department of Pathology, Paris, France.
  23. Didier Surdez: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  24. Nicolas Servant: PSL Research University, Institut Curie Research Center, INSERM U900, Paris, France; MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France.
  25. Julie Helft: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  26. Christine Sedlik: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  27. Stéphanie Puget: AP-HP, Necker Hospital, Department of Neurosurgery, Paris, France.
  28. Philippe Benaroch: PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France.
  29. Olivier Delattre: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
  30. Joshua J Waterfall: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France. Electronic address: joshua.waterfall@curie.fr.
  31. Eliane Piaggio: PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. Electronic address: eliane.piaggio@curie.fr.
  32. Franck Bourdeaut: PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. Electronic address: franck.bourdeaut@curie.fr.
PMID: 31708437 DOI: 10.1016/j.ccell.2019.10.008

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.

Keywords

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

MeSH Term

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

Chemicals

Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Nuclear Proteins
Transcription Factors
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 58

Word Cloud

Created with Highcharts 10.0.0TtumorsRTsRNAsequencingcellsRhabdoidpediatricSMARCB1SWI/SNFimmunereceptorendogenoustumorgenomicallysimplecancersdrivenbiallelicinactivationleadingchromatinremodelercomplexdeficiencyComprehensiveevaluationinfiltrateshumanmiceincludingimmunohistochemistrybulkDNAmethylationprofilingstudiesshowedhighrateinfiltratedmyeloidSingle-cellscRNAT cellhighlightedheterogeneityrevealedtherapeuticallytargetableexhaustedeffectorclonallyexpandedtissueresidentmemoryCD8subpopulationslikelyrepresentingtumor-specificCheckpointblockadetherapyexperimentalRTmodelinducedregressionestablisheddurableresponsesFinallyshowonemechanismmediatingimmunogenicityinvolvesSMARCB1-dependentre-expressionretrovirusesinterferon-signalingactivationClonallyExpandedCellsRevealImmunogenicityTumorsAT/RTcellretrovirusimmunotherapycancerrhabdoidsingle-cellimmunology

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