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Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8 + T cells.
- Source :
-
Nature communications [Nat Commun] 2017 Sep 15; Vol. 8 (1), pp. 562. Date of Electronic Publication: 2017 Sep 15. - Publication Year :
- 2017
-
Abstract
- The analysis of neoantigen-specific CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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.Immune checkpoint blockade (ICB) therapies can unleash anti-tumour T-cell responses. Here the authors show, by integrating MHC tetramer multiplexing, mass cytometry and high-dimensional analyses, that neoantigen-specific, tumour-infiltrating T cells are highly heterogeneous and are subjected to ICB modulations.
- Subjects :
- Animals
Antineoplastic Agents, Immunological pharmacology
CD8-Positive T-Lymphocytes drug effects
CTLA-4 Antigen antagonists & inhibitors
Immunophenotyping
Immunotherapy
Lymphocytes, Tumor-Infiltrating drug effects
Methylcholanthrene toxicity
Mice
Programmed Cell Death 1 Receptor antagonists & inhibitors
Sarcoma, Experimental chemically induced
Antigens, Neoplasm immunology
CD8-Positive T-Lymphocytes immunology
Lymphocytes, Tumor-Infiltrating immunology
Sarcoma, Experimental immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28916749
- Full Text :
- https://doi.org/10.1038/s41467-017-00627-z