Program death receptor-1 (PD-1) and T-cell
immunoglobulin and
mucin domain-containing protein-3 (Tim-3) play an important role in tumor immune evasion. PD-1 blockade could produce an effective anti-
tumor effect but the response rate was low due to lacking of tumor infiltrating lymphocytes (TILs) and existing of other negative regulatory pathways.
Streptavidin(SA)-
GM-CSF surface-anchored
tumor cells
vaccine could induce specific anti-
tumor immune response. However, this
vaccine failed to induce regression of established
tumor because it also up-regulated PD-1 expression on
tumor cells dependent on IFNγ and up-regulated PD-1/Tim-3 expression on CD8+ TILs. Subsets of CD8+ TILs assay showed that PD-1 expression was closely associated with CD8+ TILs exhaustion, and Tim-3 expression was closely correlated with secretion function but not proliferation of CD8+ TILs. Sequential administration of anti-PD-1 and anti-Tim-3 could further improve the efficacy of SA-
GM-CSF-anchored vaccine therapy, and
tumor regression was noted in over 50%. This triple
therapy improves the specific cytotoxic activity and decreased the apoptosis of CD8+ TILs. These findings indicated that this triple
therapy could induce a more robust anti-
tumor immune response.