Vaccines targeting helper T cells for cancer immunotherapy

There are compelling arguments for designing cancer vaccines specifically to induce CD4⁺ helper T cell responses. Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4⁺ T cells in effective antitumor immunity and reveal that CD4⁺ T cells induce more durable immune-mediated tumor control than CD8⁺ T cells. CD4⁺ T cells promote antitumor immunity by numerous mechanisms including enhancing antigen presentation, co-stimulation, T cell homing, T cell activation, and effector function. These effects are mediated at sites of T cell priming and at the tumor microenvironment. Several cancer vaccine approaches induce durable CD4⁺ T cell responses and have promising clinical activity. Future work should further optimize vaccine adjuvants and combination therapies incorporating helper peptide vaccines.