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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...

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Autores principales: Magen, Assaf, Nie, Jia, Ciucci, Thomas, Tamoutounour, Samira, Zhao, Yongmei, Mehta, Monika, Tran, Bao, McGavern, Dorian B., Hannenhalli, Sridhar, Bosselut, Rémy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
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.
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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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