Vaccines targeting helper T cells for cancer immunotherapy

•Activated CD4+ helper T cells support DC activation by expression of CD40L.•CD4+ helper T cells enhance antigen presentation and MHC expression.•Vaccines incorporating epitopes for helper T cells induce epitope spreading.•CD4+ T cells activated by vaccines support expansion of CD8 T cells in the tumor.•Helper peptide vaccines have clinical activity for breast cancer and melanoma.

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.

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