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Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells

Author

Listed:
  • M. Fehlings

    (Singapore Immunology Network (SIgN))

  • Y. Simoni

    (Singapore Immunology Network (SIgN))

  • H. L. Penny

    (Singapore Immunology Network (SIgN))

  • E. Becht

    (Singapore Immunology Network (SIgN))

  • C. Y. Loh

    (Singapore Immunology Network (SIgN))

  • M. M. Gubin

    (Washington University in St. Louis)

  • J. P. Ward

    (Washington University in St. Louis)

  • S. C. Wong

    (Singapore Immunology Network (SIgN))

  • R. D. Schreiber

    (Washington University in St. Louis)

  • E. W. Newell

    (Singapore Immunology Network (SIgN))

Abstract

The analysis of neoantigen-specific CD8+ T cells in tumour-bearing individuals is challenging due to the small pool of tumour antigen-specific T cells. Here we show that mass cytometry with multiplex combinatorial tetramer staining can identify and characterize neoantigen-specific CD8+ T cells in mice bearing T3 methylcholanthrene-induced sarcomas that are susceptible to checkpoint blockade immunotherapy. Among 81 candidate antigens tested, we identify T cells restricted to two known neoantigens simultaneously in tumours, spleens and lymph nodes in tumour-bearing mice. High-dimensional phenotypic profiling reveals that antigen-specific, tumour-infiltrating T cells are highly heterogeneous. We further show that neoantigen-specific T cells display a different phenotypic profile in mice treated with anti-CTLA-4 or anti-PD-1 immunotherapy, whereas their peripheral counterparts are not affected by the treatments. Our results provide insights into the nature of neoantigen-specific T cells and the effects of checkpoint blockade immunotherapy.

Suggested Citation

  • M. Fehlings & Y. Simoni & H. L. Penny & E. Becht & C. Y. Loh & M. M. Gubin & J. P. Ward & S. C. Wong & R. D. Schreiber & E. W. Newell, 2017. "Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00627-z
    DOI: 10.1038/s41467-017-00627-z
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