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Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells
Most current tumor immunotherapy strategies leverage cytotoxic CD8(+) T cells. Despite evidence for clinical potential of CD4(+) tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the res...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934378/ https://www.ncbi.nlm.nih.gov/pubmed/31801070 http://dx.doi.org/10.1016/j.celrep.2019.10.131 |
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author | Magen, Assaf Nie, Jia Ciucci, Thomas Tamoutounour, Samira Zhao, Yongmei Mehta, Monika Tran, Bao McGavern, Dorian B. Hannenhalli, Sridhar Bosselut, Rémy |
author_facet | Magen, Assaf Nie, Jia Ciucci, Thomas Tamoutounour, Samira Zhao, Yongmei Mehta, Monika Tran, Bao McGavern, Dorian B. Hannenhalli, Sridhar Bosselut, Rémy |
author_sort | Magen, Assaf |
collection | PubMed |
description | Most current tumor immunotherapy strategies leverage cytotoxic CD8(+) T cells. Despite evidence for clinical potential of CD4(+) tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific CD4(+) TILs and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identify TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy. Our study provides a proof-of-concept methodology to characterize tumor-specific CD4(+) T cell effector programs. Targeting these programs should help improve immunotherapy strategies. |
format | Online Article Text |
id | pubmed-6934378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-69343782019-12-27 Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells Magen, Assaf Nie, Jia Ciucci, Thomas Tamoutounour, Samira Zhao, Yongmei Mehta, Monika Tran, Bao McGavern, Dorian B. Hannenhalli, Sridhar Bosselut, Rémy Cell Rep Article Most current tumor immunotherapy strategies leverage cytotoxic CD8(+) T cells. Despite evidence for clinical potential of CD4(+) tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific CD4(+) TILs and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identify TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy. Our study provides a proof-of-concept methodology to characterize tumor-specific CD4(+) T cell effector programs. Targeting these programs should help improve immunotherapy strategies. 2019-12-03 /pmc/articles/PMC6934378/ /pubmed/31801070 http://dx.doi.org/10.1016/j.celrep.2019.10.131 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Magen, Assaf Nie, Jia Ciucci, Thomas Tamoutounour, Samira Zhao, Yongmei Mehta, Monika Tran, Bao McGavern, Dorian B. Hannenhalli, Sridhar Bosselut, Rémy Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells |
title | Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells |
title_full | Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells |
title_fullStr | Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells |
title_full_unstemmed | Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells |
title_short | Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells |
title_sort | single-cell profiling defines transcriptomic signatures specific to tumor-reactive versus virus-responsive cd4(+) t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934378/ https://www.ncbi.nlm.nih.gov/pubmed/31801070 http://dx.doi.org/10.1016/j.celrep.2019.10.131 |
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