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ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Immune checkpoint inhibitors (ICIs) are increasingly being used to manage multiple tumor types. Unfortunately, immune-related adverse events affect up to 60% of recipients, often leading to treatment discontinuation in settings where few alternative cancer therapies may be available. Checkpoint inhi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432652/ https://www.ncbi.nlm.nih.gov/pubmed/37586769 http://dx.doi.org/10.1136/jitc-2023-007358 |
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author | Mann, Jacqueline E Lucca, Liliana Austin, Matthew R Merkin, Ross D Robert, Marie E Al Bawardy, Badr Raddassi, Khadir Aizenbud, Lilach Joshi, Nikhil S Hafler, David A Abraham, Clara Herold, Kevan C Kluger, Harriet M |
author_facet | Mann, Jacqueline E Lucca, Liliana Austin, Matthew R Merkin, Ross D Robert, Marie E Al Bawardy, Badr Raddassi, Khadir Aizenbud, Lilach Joshi, Nikhil S Hafler, David A Abraham, Clara Herold, Kevan C Kluger, Harriet M |
author_sort | Mann, Jacqueline E |
collection | PubMed |
description | Immune checkpoint inhibitors (ICIs) are increasingly being used to manage multiple tumor types. Unfortunately, immune-related adverse events affect up to 60% of recipients, often leading to treatment discontinuation in settings where few alternative cancer therapies may be available. Checkpoint inhibitor induced colitis (ICI-colitis) is a common toxicity for which the underlying mechanisms are poorly defined. To better understand the changing colon-specific and peripheral immune environments over the course of progression and treatment of colitis, we collected blood and colon tissue from a patient with Merkel cell carcinoma who developed colitis on treatment with pembrolizumab. We performed single-cell RNA sequencing and T-cell receptor sequencing on samples collected before, during and after pembrolizumab and after various interventions to mitigate toxicity. We report T-cells populations defined by cytotoxicity, memory, and proliferation markers at various stages of colitis. We show preferential depletion of CD8+ T cells with biologic therapy and nominate both circulating and colon-resident T-cell subsets as potential drivers of inflammation and response to immune suppression. Our findings highlight the need for further exploration of the colon immune environment and rationalize future studies evaluating biologics for ICI-colitis, including in the context of ICI re-challenge. |
format | Online Article Text |
id | pubmed-10432652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-104326522023-08-18 ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis Mann, Jacqueline E Lucca, Liliana Austin, Matthew R Merkin, Ross D Robert, Marie E Al Bawardy, Badr Raddassi, Khadir Aizenbud, Lilach Joshi, Nikhil S Hafler, David A Abraham, Clara Herold, Kevan C Kluger, Harriet M J Immunother Cancer Case Report Immune checkpoint inhibitors (ICIs) are increasingly being used to manage multiple tumor types. Unfortunately, immune-related adverse events affect up to 60% of recipients, often leading to treatment discontinuation in settings where few alternative cancer therapies may be available. Checkpoint inhibitor induced colitis (ICI-colitis) is a common toxicity for which the underlying mechanisms are poorly defined. To better understand the changing colon-specific and peripheral immune environments over the course of progression and treatment of colitis, we collected blood and colon tissue from a patient with Merkel cell carcinoma who developed colitis on treatment with pembrolizumab. We performed single-cell RNA sequencing and T-cell receptor sequencing on samples collected before, during and after pembrolizumab and after various interventions to mitigate toxicity. We report T-cells populations defined by cytotoxicity, memory, and proliferation markers at various stages of colitis. We show preferential depletion of CD8+ T cells with biologic therapy and nominate both circulating and colon-resident T-cell subsets as potential drivers of inflammation and response to immune suppression. Our findings highlight the need for further exploration of the colon immune environment and rationalize future studies evaluating biologics for ICI-colitis, including in the context of ICI re-challenge. BMJ Publishing Group 2023-08-16 /pmc/articles/PMC10432652/ /pubmed/37586769 http://dx.doi.org/10.1136/jitc-2023-007358 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Case Report Mann, Jacqueline E Lucca, Liliana Austin, Matthew R Merkin, Ross D Robert, Marie E Al Bawardy, Badr Raddassi, Khadir Aizenbud, Lilach Joshi, Nikhil S Hafler, David A Abraham, Clara Herold, Kevan C Kluger, Harriet M ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
title | ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
title_full | ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
title_fullStr | ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
title_full_unstemmed | ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
title_short | ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
title_sort | scrna-seq defines dynamic t-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432652/ https://www.ncbi.nlm.nih.gov/pubmed/37586769 http://dx.doi.org/10.1136/jitc-2023-007358 |
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