Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-00627-z
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dc.titleCheckpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells
dc.contributor.authorFehlings, M
dc.contributor.authorSimoni, Y
dc.contributor.authorPenny, H.L
dc.contributor.authorBecht, E
dc.contributor.authorLoh, C.Y
dc.contributor.authorGubin, M.M
dc.contributor.authorWard, J.P
dc.contributor.authorWong, S.C
dc.contributor.authorSchreiber, R.D
dc.contributor.authorNewell, E.W
dc.date.accessioned2020-10-20T10:23:47Z
dc.date.available2020-10-20T10:23:47Z
dc.date.issued2017
dc.identifier.citationFehlings, 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
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178577
dc.description.abstractThe 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).
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subject3 methylcholanthrene
dc.subjectCD27 antigen
dc.subjectCD38 antigen
dc.subjectchemokine receptor CXCR3
dc.subjectcytotoxic T lymphocyte antigen 4 antibody
dc.subjectgranzyme B
dc.subjecthepatitis A virus cellular receptor 2
dc.subjectHermes antigen
dc.subjectinterleukin 2 receptor alpha
dc.subjectinterleukin 7 receptor
dc.subjectL selectin
dc.subjectmonoclonal antibody
dc.subjectprogrammed death 1 antibody
dc.subjectprogrammed death 1 ligand 1
dc.subjecttetramer
dc.subjectunclassified drug
dc.subject3 methylcholanthrene
dc.subjectcytotoxic T lymphocyte antigen 4
dc.subjectimmunological antineoplastic agent
dc.subjectprogrammed death 1 receptor
dc.subjecttumor antigen
dc.subjectantigen
dc.subjectcancer
dc.subjectcells and cell components
dc.subjectdisease treatment
dc.subjectheterogeneity
dc.subjectimmune system
dc.subjectphenotype
dc.subjectrodent
dc.subjecttumor
dc.subjectalgorithm
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectCD8+ T lymphocyte
dc.subjectcell differentiation
dc.subjectcell infiltration
dc.subjectcell migration
dc.subjectcomparative study
dc.subjectcontrolled study
dc.subjectflow cytometry
dc.subjectgene expression
dc.subjectimmunocompetent cell
dc.subjectimmunotherapy
dc.subjectlymph node
dc.subjectmale
dc.subjectmass cytometry
dc.subjectmelanoma
dc.subjectmouse
dc.subjectneoplasm
dc.subjectnonhuman
dc.subjectphenotype
dc.subjectprotein expression
dc.subjectsarcoma
dc.subjecttumor immunity
dc.subjectupregulation
dc.subjectwild type
dc.subjectanimal
dc.subjectantagonists and inhibitors
dc.subjectCD8+ T lymphocyte
dc.subjectchemically induced
dc.subjectdrug effects
dc.subjectexperimental sarcoma
dc.subjectimmunology
dc.subjectimmunophenotyping
dc.subjectimmunotherapy
dc.subjecttumor associated leukocyte
dc.subjectMurinae
dc.subjectMus
dc.subjectAnimals
dc.subjectAntigens, Neoplasm
dc.subjectAntineoplastic Agents, Immunological
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCTLA-4 Antigen
dc.subjectImmunophenotyping
dc.subjectImmunotherapy
dc.subjectLymphocytes, Tumor-Infiltrating
dc.subjectMethylcholanthrene
dc.subjectMice
dc.subjectProgrammed Cell Death 1 Receptor
dc.subjectSarcoma, Experimental
dc.typeArticle
dc.contributor.departmentMICROBIOLOGY AND IMMUNOLOGY
dc.description.doi10.1038/s41467-017-00627-z
dc.description.sourcetitleNature Communications
dc.description.volume8
dc.description.issue1
dc.description.page562
dc.published.statepublished
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