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Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells

Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell re...

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Autores principales: Lucca, Liliana E., Axisa, Pierre-Paul, Lu, Benjamin, Harnett, Brian, Jessel, Shlomit, Zhang, Le, Raddassi, Khadir, Zhang, Lin, Olino, Kelly, Clune, James, Singer, Meromit, Kluger, Harriet M., Hafler, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933991/
https://www.ncbi.nlm.nih.gov/pubmed/33651881
http://dx.doi.org/10.1084/jem.20200921
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author Lucca, Liliana E.
Axisa, Pierre-Paul
Lu, Benjamin
Harnett, Brian
Jessel, Shlomit
Zhang, Le
Raddassi, Khadir
Zhang, Lin
Olino, Kelly
Clune, James
Singer, Meromit
Kluger, Harriet M.
Hafler, David A.
author_facet Lucca, Liliana E.
Axisa, Pierre-Paul
Lu, Benjamin
Harnett, Brian
Jessel, Shlomit
Zhang, Le
Raddassi, Khadir
Zhang, Lin
Olino, Kelly
Clune, James
Singer, Meromit
Kluger, Harriet M.
Hafler, David A.
author_sort Lucca, Liliana E.
collection PubMed
description Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed at the single-cell level from matched tumor and blood from patients with metastatic melanoma. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by tumor-exclusive T cells. Finally, genes associated with a high degree of blood–tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs have unique transcriptional patterns that may have utility for the interrogation of T cell function in cancer immunotherapy.
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spelling pubmed-79339912021-10-05 Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells Lucca, Liliana E. Axisa, Pierre-Paul Lu, Benjamin Harnett, Brian Jessel, Shlomit Zhang, Le Raddassi, Khadir Zhang, Lin Olino, Kelly Clune, James Singer, Meromit Kluger, Harriet M. Hafler, David A. J Exp Med Brief Definitive Report Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed at the single-cell level from matched tumor and blood from patients with metastatic melanoma. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by tumor-exclusive T cells. Finally, genes associated with a high degree of blood–tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs have unique transcriptional patterns that may have utility for the interrogation of T cell function in cancer immunotherapy. Rockefeller University Press 2021-03-02 /pmc/articles/PMC7933991/ /pubmed/33651881 http://dx.doi.org/10.1084/jem.20200921 Text en © 2021 Lucca et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Lucca, Liliana E.
Axisa, Pierre-Paul
Lu, Benjamin
Harnett, Brian
Jessel, Shlomit
Zhang, Le
Raddassi, Khadir
Zhang, Lin
Olino, Kelly
Clune, James
Singer, Meromit
Kluger, Harriet M.
Hafler, David A.
Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
title Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
title_full Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
title_fullStr Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
title_full_unstemmed Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
title_short Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
title_sort circulating clonally expanded t cells reflect functions of tumor-infiltrating t cells
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933991/
https://www.ncbi.nlm.nih.gov/pubmed/33651881
http://dx.doi.org/10.1084/jem.20200921
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