Vaccine stimulated NK cells and CD4+ T cells control tumor burden while an immunosuppressive tumor microenvironment drives CD8+ TIL exhaustion. a CD4+ T cells, CD8+ T cells and NK cells infiltrate TRAMP-C1 tumors, b mice were depleted of either NK cells, CD4+ T cells or CD8+ T cells. Tumor growth in NK depleted mice (left panel), CD4+ T cell depleted mice (middle panel) and CD8+ T cell depleted mice (right panel), c time-course of representative CD8+PD1+TIM3+ TIL profiles d Proportion of PD1+TIM3+ TILs (open squares) as a function of time and tumor size (filled circles). Data are presented as mean ± SEM where n = 9–10 mice/group from one representative experiment of two equivalent experiments. Statistical significance in tumor growth was determined using a two-way ANOVA. p < 0.01** and p < 0.001***. IMX = ISCOMATRIX® adjuvant