Melssen and Slingluff summarize the multiple roles of CD4+ helper T cells in antitumor immunity and cancer vaccines, including antigen-induced IFN-γ production, co-stimulation of dendritic cells to improve efficacy of CD8+ T cell priming, T cell homing to the tumor via cytokine stimulation, T cell activation, anti-tumor effector function, and optimal CD8+ memory T cell formation.
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.
Author Info: (1) University of Virginia, Department of Surgery and University of Virginia Cancer Center, PO Box 800709, Charlottesville, VA, USA. (2) University of Virginia, Department of Surge
Author Info: (1) University of Virginia, Department of Surgery and University of Virginia Cancer Center, PO Box 800709, Charlottesville, VA, USA. (2) University of Virginia, Department of Surgery and University of Virginia Cancer Center, PO Box 800709, Charlottesville, VA, USA. Electronic address: cls8h@virginia.edu.
