Combination ipilimumab and nivolumab therapy induces a rise in
circulating activated memory CD8+ and
CD4+ T cells and activated memory gut-homing
CD8+ T cells.
We sought to determine if changes in the PBMC compartment could be used
as biomarkers for the changes seen in gastrointestinal tissue-derived
lymphocytes in IN-COL. Treatment with combination ipilimumab and
nivolumab therapy was associated with a rise in activated memory
(CD45RA-HLA-DR+CD38+)
CD8+T cells, regardless of the presence of colitis. In
the IN-COL group the proportion of these cells were significantly
elevated at the point of colitis (11% of memory CD8+T cells) compared with baseline (0%; p<0.01; Figure 3a-b).
There was also a significant rise in the proportion of activated memory
CD8+ T cells in the IN-NAE group following therapy
(8% of memory CD8+ T cells at week 7-10 compared with 1% at baseline;
p<0.01; Figure 3a). The proportion of these cells did not
differ between patients with active UC and healthy volunteers.
Similarly, combination ipilimumab and nivolumab therapy was also
associated with a rise in activated memory
(CD45RA-HLA-DR+CD38+)
CD4+ T cells, regardless of the presence of colitis.
The IN-COL group had 4% of activated memory CD4+ T
cells compared with 0% at baseline (p<0.01; Figure 3c-d).
Patients in the IN-NAE group also displayed an increased proportion of
activated memory CD4+ T cells following therapy (5%
at week 7-10 compared with 1% at baseline; p<0.01; Figure
3c). The proportion of these cells did not differ between patients with
active UC and healthy volunteers.
Absence of non-specific background staining for HLA-DR and CD38 was
demonstrated using isotype control antibodies (Supplementary Figure 2a).