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Tytuł:
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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.
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Autorzy:
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Sasson SC; Translational Gastroenterology Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Zaunders JJ; Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia.
Nahar K; Melanoma Institute Australia and The University of Sydney, Sydney, Australia.
Munier CML; The Kirby Institute, University of New South Wales, Sydney, Australia.
Fairfax BP; Department of Oncology, Churchill Hospital, Oxford, UK.; Department of Oncology, University of Oxford, Oxford, UK.; MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Olsson-Brown A; The Clatterbridge Cancer Centre NHS Foundation Trust and Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Jolly C; The Clatterbridge Cancer Centre NHS Foundation Trust and Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Read SA; Westmead Institute of Medical Research, Sydney, Australia.; Western Sydney University, Sydney, Australia.
Ahlenstiel G; Westmead Institute of Medical Research, Sydney, Australia.; Department of Gastroenterology, Blacktown Hospital, Sydney, Australia.
Palendira U; Discipline of Infectious Diseases and Immunology, The University of Sydney, Sydney, Australia.
Scolyer RA; Melanoma Institute Australia and The University of Sydney, Sydney, Australia.; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
Carlino MS; Melanoma Institute Australia and The University of Sydney, Sydney, Australia.; Department of Medical Oncology, Westmead and Blacktown Hospitals, Sydney, Australia.
Payne MJ; Department of Oncology, Churchill Hospital, Oxford, UK.
Cheung VTF; Translational Gastroenterology Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Gupta T; Translational Gastroenterology Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Klenerman P; Translational Gastroenterology Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Peter Medawar Building of Pathogen Research, University of Oxford, Oxford, UK.
Long GV; Melanoma Institute Australia and The University of Sydney, Sydney, Australia.; Department of Medical Oncology, Royal North Shore Hospital and Mater Hospitals, Sydney, Australia.
Brain O; Translational Gastroenterology Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Department of Gastroenterology, John Radcliffe Hospital, Oxford, UK.
Menzies AM; Melanoma Institute Australia and The University of Sydney, Sydney, Australia.; Department of Medical Oncology, Royal North Shore Hospital and Mater Hospitals, Sydney, Australia.
Kelleher AD; Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia.; The Kirby Institute, University of New South Wales, Sydney, Australia.
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Źródło:
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Clinical and experimental immunology [Clin Exp Immunol] 2020 Dec; Vol. 202 (3), pp. 335-352. Date of Electronic Publication: 2020 Aug 19.
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Typ publikacji:
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Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2022- : Oxford : Oxford University Press
Original Publication: Oxford : Blackwell Scientific Publications
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MeSH Terms:
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CD8-Positive T-Lymphocytes*/immunology
CD8-Positive T-Lymphocytes*/pathology
Colitis*/chemically induced
Colitis*/immunology
Colitis*/pathology
Intestinal Mucosa*/immunology
Intestinal Mucosa*/pathology
Mucosal-Associated Invariant T Cells*/immunology
Mucosal-Associated Invariant T Cells*/pathology
T-Lymphocytes, Regulatory*/immunology
T-Lymphocytes, Regulatory*/pathology
Ipilimumab/*adverse effects
Nivolumab/*adverse effects
Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Ipilimumab/administration & dosage ; Male ; Middle Aged ; Nivolumab/administration & dosage
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Grant Information:
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109965/Z/15/Z United Kingdom WT_ Wellcome Trust; 201488/Z/16/Z United Kingdom WT_ Wellcome Trust; MR/N025989/1 United Kingdom MRC_ Medical Research Council
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Contributed Indexing:
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Keywords: MAIT cells; checkpoint inhibitor; colitis; ipilimumab; nivolumab
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Substance Nomenclature:
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0 (Ipilimumab)
31YO63LBSN (Nivolumab)
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Entry Date(s):
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Date Created: 20200801 Date Completed: 20210518 Latest Revision: 20221005
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Update Code:
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20240104
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PubMed Central ID:
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PMC7670140
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DOI:
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10.1111/cei.13502
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PMID:
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32734627
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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 (T reg ). 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 T reg , 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.
(© 2020 The Authors. Clinical & Experimental Immunology published by John Wiley and Sons Ltd on behalf of British Society for Immunology.)
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