Unlike the direct cytotoxic ability of CD8+ T lymphocytes (CTLs) that have long been considered the primary population to mediate tumor rejection in Immune Checkpoint blockade (ICB) and adoptive cell therapy (ACT), the antitumoral potency of CD4+ T cells is mainly mediated by initiating macrophage polarization, natural killer (NK) cell recruitment, and cross priming to CTLs 2-4. The gene discussed is CD4; the disease is neoplasm.