Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells
Open Access
- 15 September 2017
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 8 (1) , 1-12
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.Keywords
This publication has 48 references indexed in Scilit:
- MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint BlockadeImmunity, 2016
- Mutant MHC class II epitopes drive therapeutic immune responses to cancerNature, 2015
- Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancerScience, 2015
- Consensus nomenclature for CD8+T cell phenotypes in cancerOncoImmunology, 2015
- High-dimensional analysis of the murine myeloid cell systemNature Immunology, 2014
- Combinatorial tetramer staining and mass cytometry analysis facilitate T-cell epitope mapping and characterizationNature Biotechnology, 2013
- Immunodominance: A pivotal principle in host response to viral infectionsClinical Immunology, 2012
- Cytometry by Time-of-Flight Shows Combinatorial Cytokine Expression and Virus-Specific Cell Niches within a Continuum of CD8+ T Cell PhenotypesImmunity, 2012
- Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impairedBlood, 2009
- Simultaneous detection of many T-cell specificities using combinatorial tetramer stainingNature Methods, 2009