Collectively, this work has supported a direct cytotoxic role for CD4+ T cells in enhanced anti-tumor immunity after modulation of specific immunity checkpoints (CTLA-4 blockade, OX40 agonism), driven by the effects of TFs that do not involve TBET/Th1 polarization, but may differ depending on the therapeutic context. This evidence concerns the gene TNFRSF4 and neoplasm.