Please use this identifier to cite or link to this item: 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
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