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https://doi.org/10.1038/s41467-017-00627-z
Title: | Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells | Authors: | Fehlings, M Simoni, Y Penny, H.L Becht, E Loh, C.Y Gubin, M.M Ward, J.P Wong, S.C Schreiber, R.D Newell, E.W |
Keywords: | 3 methylcholanthrene CD27 antigen CD38 antigen chemokine receptor CXCR3 cytotoxic T lymphocyte antigen 4 antibody granzyme B hepatitis A virus cellular receptor 2 Hermes antigen interleukin 2 receptor alpha interleukin 7 receptor L selectin monoclonal antibody programmed death 1 antibody programmed death 1 ligand 1 tetramer unclassified drug 3 methylcholanthrene cytotoxic T lymphocyte antigen 4 immunological antineoplastic agent programmed death 1 receptor tumor antigen antigen cancer cells and cell components disease treatment heterogeneity immune system phenotype rodent tumor algorithm animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte cell differentiation cell infiltration cell migration comparative study controlled study flow cytometry gene expression immunocompetent cell immunotherapy lymph node male mass cytometry melanoma mouse neoplasm nonhuman phenotype protein expression sarcoma tumor immunity upregulation wild type animal antagonists and inhibitors CD8+ T lymphocyte chemically induced drug effects experimental sarcoma immunology immunophenotyping immunotherapy tumor associated leukocyte Murinae Mus Animals Antigens, Neoplasm Antineoplastic Agents, Immunological CD8-Positive T-Lymphocytes CTLA-4 Antigen Immunophenotyping Immunotherapy Lymphocytes, Tumor-Infiltrating Methylcholanthrene Mice Programmed Cell Death 1 Receptor Sarcoma, Experimental |
Issue Date: | 2017 | Publisher: | Nature Publishing Group | Citation: | Fehlings, M, Simoni, Y, Penny, H.L, Becht, E, Loh, C.Y, Gubin, M.M, Ward, J.P, Wong, S.C, Schreiber, R.D, Newell, E.W (2017). Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells. Nature Communications 8 (1) : 562. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-00627-z | Rights: | Attribution 4.0 International | 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. © 2017 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/178577 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-017-00627-z | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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