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Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis

Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patien...

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Autores principales: Arriola, Edurne, Wheater, Matthew, Lopez, Maria Antonette, Thomas, Gareth, Ottensmeier, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048766/
https://www.ncbi.nlm.nih.gov/pubmed/27757302
http://dx.doi.org/10.1080/2162402X.2016.1209615
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author Arriola, Edurne
Wheater, Matthew
Lopez, Maria Antonette
Thomas, Gareth
Ottensmeier, Christian
author_facet Arriola, Edurne
Wheater, Matthew
Lopez, Maria Antonette
Thomas, Gareth
Ottensmeier, Christian
author_sort Arriola, Edurne
collection PubMed
description Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8(+), FoxP3, and granzyme B (GzmB) in colonic biopsies from 20 patients with ipilimumab-related colitis. We assessed 10 cases with normal colon biopsies for comparison. In eight cases (four on steroids only, four on steroids and infliximab), we evaluated two sequential biopsies. We observed that CD8(+), FoxP3(+), and GzmB T cell counts were significantly higher in patients with ipilimumab-related colitis compared to normal colon (p < 0.0001). Patients who required infliximab for the resolution of their colitis had a significantly higher CD8(+)/FoxP3 ratio than those treated only with steroids and this correlated with clinical severity. The analysis of repeat samples revealed that resolution of the colitis was associated with a decrease in CD8(+) and FoxP3(+) cells both in patients treated with steroids and infliximab. Our data suggest that counts of cytotoxic T cells and Tregs in the colonic mucosa from patients with ipilimumab-related colitis correlate with clinical findings and may predict severity and guide management.
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spelling pubmed-50487662016-10-18 Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis Arriola, Edurne Wheater, Matthew Lopez, Maria Antonette Thomas, Gareth Ottensmeier, Christian Oncoimmunology Original Research Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8(+), FoxP3, and granzyme B (GzmB) in colonic biopsies from 20 patients with ipilimumab-related colitis. We assessed 10 cases with normal colon biopsies for comparison. In eight cases (four on steroids only, four on steroids and infliximab), we evaluated two sequential biopsies. We observed that CD8(+), FoxP3(+), and GzmB T cell counts were significantly higher in patients with ipilimumab-related colitis compared to normal colon (p < 0.0001). Patients who required infliximab for the resolution of their colitis had a significantly higher CD8(+)/FoxP3 ratio than those treated only with steroids and this correlated with clinical severity. The analysis of repeat samples revealed that resolution of the colitis was associated with a decrease in CD8(+) and FoxP3(+) cells both in patients treated with steroids and infliximab. Our data suggest that counts of cytotoxic T cells and Tregs in the colonic mucosa from patients with ipilimumab-related colitis correlate with clinical findings and may predict severity and guide management. Taylor & Francis 2016-07-15 /pmc/articles/PMC5048766/ /pubmed/27757302 http://dx.doi.org/10.1080/2162402X.2016.1209615 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Original Research
Arriola, Edurne
Wheater, Matthew
Lopez, Maria Antonette
Thomas, Gareth
Ottensmeier, Christian
Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
title Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
title_full Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
title_fullStr Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
title_full_unstemmed Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
title_short Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
title_sort evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048766/
https://www.ncbi.nlm.nih.gov/pubmed/27757302
http://dx.doi.org/10.1080/2162402X.2016.1209615
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