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).