An agonist CD40 antibody based immunotherapy was less efficient at promoting tumor regression in elderly mice, which may be due to: (i) failure of elderly CD8+ T cells to up-regulate perforin, and (ii) increased expression of multiple regulatory markers on CD11c+ cells and T cells in elderly tumor-draining lymph nodes (including CD73, PD-1, ICOS, LAG-3, and TGF-β). The gene discussed is ICOS; the disease is neoplasm.