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
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
by 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, characterised 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 (Figure1).