Requirement of tumor-associated antigen-specific CD4+ T cells for an efficient dendritic cell vaccine in antitumor immunotherapy

Evaluation of: Aarntzen EH, De Vries IJ, Lesterhuis WJ et al. Targeting CD4(+) T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination. Cancer Res. 73(1), 19-29 (2012). The induction of antitumor immune responses in patients is one of the most sought-after goals in cancer treatment. The proposed clinical approach is to use autologous mature dendritic cells (DCs) loaded with class I peptides from tumor-associated antigens (TAAs), as DCs are the most efficient immune cells to generate strong and specific cytotoxic CD8(+) T-lymphocyte (CTL) responses. To optimize DC-based cancer vaccines, Aarntzen et al. evaluated the necessity to stimulate TAA-specific CD4(+) T-helper cells to reinforce antitumor CTL responses. They demonstrated that intranodal injection of DCs pulsed with class I-and II-restricted TAA epitopes increases TAA-specific CTL responses and induces better clinical responses in stage III/IV melanoma patients than the use of DCs pulsed with class I-restricted TAA epitopes alone. This study highlights the interest of concomitant stimulation of TAA-specific CD4(+) and CD8(+) T cells for DC-based antitumor immunotherapy.