Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis
| Autor: | Anna Olsson-Brown, A.M. Menzies, K. Nahar, Cheung Vtf., C. Jolly, Benjamin P. Fairfax, Golo Ahlenstiel, Umaimainthan Palendira, Anthony D. Kelleher, Miranda Payne, Richard A. Scolyer, Munier Cml., Matteo S. Carlino, Scott A. Read, Tarun Gupta, Georgina V. Long, Sarah C. Sasson, Oliver Brain, John Zaunders, Paul Klenerman |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty colitis T cell Immunology MAIT cells Ipilimumab CD8-Positive T-Lymphocytes Peripheral blood mononuclear cell T-Lymphocytes Regulatory Mucosal-Associated Invariant T Cells Flow cytometry 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Humans Colitis Intestinal Mucosa Aged nivolumab medicine.diagnostic_test business.industry Original Articles Middle Aged medicine.disease Flow Cytometry Ulcerative colitis 030104 developmental biology medicine.anatomical_structure Cancer Immunology checkpoint inhibitor Female Original Article Nivolumab business CD8 030215 immunology medicine.drug |
| Zdroj: | Clinical and Experimental Immunology |
| ISSN: | 1365-2249 |
| Popis: | Mucosal‐associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy‐related colitis in a pathology distinct from ulcerative colitis. Summary The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab‐associated colitis (IN‐COL) by measuring gut‐derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN‐COL, IN‐treated with no adverse‐events (IN‐NAE), ulcerative colitis (UC) and healthy volunteers using flow cytometry. In the gastrointestinal‐derived cells we found high levels of activated CD8+ T cells and mucosal‐associated invariant T (MAIT) cells in IN‐COL, changes that were not evident in IN‐NAE or UC. UC, but not IN‐C, was associated with a high proportion of regulatory T cells (Treg). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN‐COL patients compared with IN‐NAE in one of two cohorts. UC, but not IN‐COL, was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN‐COL‐affected tissue, characterized by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg, reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on‐treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis. |
| Databáze: | OpenAIRE |
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