Figure 7.

4-1BB co-stimulation further enhances antiprogrammed cell death protein 1 (anti-PD-1)-mediated reinvigoration of exhausted CD8 tumor-infiltrating lymphocytes (TILs) from the ovary and metastatic sites. (A) In the presence of anti-CD3 antibodies, we analyzed the frequency of CTV^low CD8 TILs (proliferated CD8 TILs) in the presence of isotype or anti-PD-1 blocking antibodies, or a combination of anti-PD-1 blocking antibodies and anti-4-1BB agonistic antibodies. Representative flow cytometry plots are shown to the left, and data are presented as the stimulation index. (B–C) We evaluated changes of the functional capacities of CD8 TILs after stimulation with antibodies by intracellular staining of cytokines (interferon (IFN)-γ and tumor necrosis factor (TNF)-α). We compared three different treatment groups: isotype-treated, anti-PD-1 blocking antibodies-treated and combined treatment with anti-PD-1 blocking antibodies and anti-4-1BB agonistic antibodies. Representative flow cytometry plots are shown to the left, and data are presented as the relative ratio to the isotype-treated group, separately for the ovary (B) and metastatic sites (C). *P<0.05; **p<0.01; ***p<0.001; ****p<0.0001.