Administration of hAB21 to MC38 tumor bearing mice resulted in DC activation in the spleen and tumor that when further combined with anti-PD-1/PD-L1 therapy promoted both CD4++ and CD8+ T cell effector functions and reduced immunosuppressive CD4+ Tregs and TAMs leading to eradication of MC38 tumors and long-term, durable immunity. Here, CD4 is linked to neoplasm.