Evidence in the literature points to multiple factors influencing proper cytotoxic CD8+ T cell function including the recruitment of effector CD8+ T cell subpopulations (tumor antigen specific, granzyme B+, IFNγ+), reinvigoration of exhausted and inactivated CD8+ T cells (PD1+, LAG3+, TIM-3+, CD25-), and optimal immune microenvironment (increased CD8+ T cell / CD4+FoxP3+ T cell ratio, Th1 CD4+ T helper immune response, M1 macrophage phenotype) in GBM immunotherapy 23, 44, 53-57. The gene discussed is CD4; the disease is glioblastoma.