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Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  1. Author Correction: Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Michael D Crowther
  • Garry Dolton
  • Mateusz Legut
  • Marine E Caillaud
  • Angharad Lloyd
  • Meriem Attaf
  • Sarah A E Galloway
  • Cristina Rius
  • Colin P Farrell
  • Barbara Szomolay
  • Ann Ager
  • Alan L Parker
  • Anna Fuller
  • Marco Donia
  • James McCluskey
  • Jamie Rossjohn
  • Inge Marie Svane
  • John D Phillips
  • Andrew K Sewell
Vis graf over relationer

Human leukocyte antigen (HLA)-independent, T cell-mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR-Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.

OriginalsprogEngelsk
TidsskriftNature Immunology
Vol/bind21
Udgave nummer2
Sider (fra-til)178-185
Antal sider8
ISSN1529-2908
DOI
StatusUdgivet - feb. 2020

ID: 59227054