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

M. Fehlings, Y. Simoni, H. L. Penny, E. Becht, C. Y. Loh, M. M. Gubin, J. P. Ward, S. C. Wong, R. D. Schreiber and E. W. Newell ()
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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)

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00627-z

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