ABSTRACT
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.
Subject(s)
CD8-Positive T-Lymphocytes , Colitis , Intestinal Mucosa , Ipilimumab/adverse effects , Mucosal-Associated Invariant T Cells , Nivolumab/adverse effects , T-Lymphocytes, Regulatory , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Colitis/chemically induced , Colitis/immunology , Colitis/pathology , Female , Flow Cytometry , Humans , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Ipilimumab/administration & dosage , Male , Middle Aged , Mucosal-Associated Invariant T Cells/immunology , Mucosal-Associated Invariant T Cells/pathology , Nivolumab/administration & dosage , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/pathologyABSTRACT
PURPOSE: It is vital that surgeons undertaking oculoplastic procedures are able to show that the surgery they perform is of benefit to their patients. Not only is this fundamental to patient-centred medicine but it is also important in demonstrating cost effectiveness. There are several ways in which benefit can be measured, including clinical scales, functional ability scales, and global quality-of-life scales. The Glasgow benefit inventory (GBI) is an example of a patient-reported, questionnaire-based, post-interventional quality-of-life scale that can be used to compare a range of different treatments for a variety of conditions. METHODS: A cross-sectional study was undertaken using the GBI to score patient benefit from four commonly performed oculoplastic procedures. It was completed for 66 entropion repairs, 50 ptosis repairs, 41 ectropion repairs, and 41 external dacryocystorhinostomies (DCR). The GBI generates a scale from -100 (maximal detriment) through zero (no change) to +100 (maximal benefit). RESULTS: The total GBI scores of patients undergoing surgery for entropion, ptosis, ectropion, and external DCR were: +25.25 (95% CI 20.00-30.50, P<0.001), +24.89 (95% CI 20.04-29.73, P<0.001), +17.68 (95% CI 9.46-25.91, P<0.001), and +32.25 (95% CI 21.47-43.03, P<0.001), respectively, demonstrating a statistically significant benefit from all procedures. CONCLUSION: Patients derived significant quality-of-life benefits from the four most commonly performed oculoplastic procedures.