In the CT2A glioblastoma murine model, combination therapy employing CD40 agonists and PD-1 inhibitors significantly enhanced survival outcomes; Mechanistically, CD4+ T cells crucially maintain progenitor exhausted CD8+ T cell populations and their responsiveness to PD-1 blockade; CD40 agonism bypasses CD4+ T cell dysfunction, thereby potentiating PD-1 checkpoint therapy efficacy (31). The gene discussed is CD40; the disease is glioblastoma.