We previously performed a series of in vivo combination studies using an anti-mouse PD-1 antibody and one of five other antibodies/agents that deplete CD8+ T cells, CD4+ T cells, regulatory T (Treg) cells, natural killer (NK) cells, and tumor-associated macrophages (TAM), respectively, in four anti-PD-1 antibody-responsive syngeneic models to show that they have different mechanisms of actions under the anti-PD-1 treatment (35). The gene discussed is CD4; the disease is neoplasm.