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Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy

Our understanding of how checkpoint inhibitors (CPI) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here we analyzed peripheral T cell populations after one cycle of CPI and identified a dynamic awakening of the immune system revealed b...

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Autores principales: Valpione, Sara, Galvani, Elena, Tweedy, Joshua, Mundra, Piyushkumar A., Banyard, Antonia, Middlehurst, Philippa, Barry, Jeff, Mills, Sarah, Salih, Zena, Weightman, John, Gupta, Avinash, Gremel, Gabriela, Baenke, Franziska, Dhomen, Nathalie, Lorigan, Paul C., Marais, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046489/
https://www.ncbi.nlm.nih.gov/pubmed/32110781
http://dx.doi.org/10.1038/s43018-019-0022-x
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author Valpione, Sara
Galvani, Elena
Tweedy, Joshua
Mundra, Piyushkumar A.
Banyard, Antonia
Middlehurst, Philippa
Barry, Jeff
Mills, Sarah
Salih, Zena
Weightman, John
Gupta, Avinash
Gremel, Gabriela
Baenke, Franziska
Dhomen, Nathalie
Lorigan, Paul C.
Marais, Richard
author_facet Valpione, Sara
Galvani, Elena
Tweedy, Joshua
Mundra, Piyushkumar A.
Banyard, Antonia
Middlehurst, Philippa
Barry, Jeff
Mills, Sarah
Salih, Zena
Weightman, John
Gupta, Avinash
Gremel, Gabriela
Baenke, Franziska
Dhomen, Nathalie
Lorigan, Paul C.
Marais, Richard
author_sort Valpione, Sara
collection PubMed
description Our understanding of how checkpoint inhibitors (CPI) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here we analyzed peripheral T cell populations after one cycle of CPI and identified a dynamic awakening of the immune system revealed by T cell evolution in response to treatment. We sequenced T cell receptors (TCR) in plasma cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMC) and performed phenotypic analysis of peripheral T cell subsets from metastatic melanoma patients treated with CPI. We found that early peripheral T cell turnover and TCR repertoire dynamics identified which patients would respond to treatment. Additionally, the expansion of a subset of immune-effector peripheral T cells we call T(IE) cells correlated with response. These events are prognostic and occur within 3 weeks of starting immunotherapy, raising the potential for monitoring patients responses using minimally invasive liquid biopsies.”
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spelling pubmed-70464892020-02-27 Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy Valpione, Sara Galvani, Elena Tweedy, Joshua Mundra, Piyushkumar A. Banyard, Antonia Middlehurst, Philippa Barry, Jeff Mills, Sarah Salih, Zena Weightman, John Gupta, Avinash Gremel, Gabriela Baenke, Franziska Dhomen, Nathalie Lorigan, Paul C. Marais, Richard Nat Cancer Article Our understanding of how checkpoint inhibitors (CPI) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here we analyzed peripheral T cell populations after one cycle of CPI and identified a dynamic awakening of the immune system revealed by T cell evolution in response to treatment. We sequenced T cell receptors (TCR) in plasma cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMC) and performed phenotypic analysis of peripheral T cell subsets from metastatic melanoma patients treated with CPI. We found that early peripheral T cell turnover and TCR repertoire dynamics identified which patients would respond to treatment. Additionally, the expansion of a subset of immune-effector peripheral T cells we call T(IE) cells correlated with response. These events are prognostic and occur within 3 weeks of starting immunotherapy, raising the potential for monitoring patients responses using minimally invasive liquid biopsies.” 2020-02-10 2020-02 /pmc/articles/PMC7046489/ /pubmed/32110781 http://dx.doi.org/10.1038/s43018-019-0022-x Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Valpione, Sara
Galvani, Elena
Tweedy, Joshua
Mundra, Piyushkumar A.
Banyard, Antonia
Middlehurst, Philippa
Barry, Jeff
Mills, Sarah
Salih, Zena
Weightman, John
Gupta, Avinash
Gremel, Gabriela
Baenke, Franziska
Dhomen, Nathalie
Lorigan, Paul C.
Marais, Richard
Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
title Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
title_full Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
title_fullStr Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
title_full_unstemmed Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
title_short Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
title_sort immune-awakening revealed by peripheral t cell dynamics after one cycle of immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046489/
https://www.ncbi.nlm.nih.gov/pubmed/32110781
http://dx.doi.org/10.1038/s43018-019-0022-x
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