CD4 and cancer: Recently, research focus has shifted to generate cancer vaccines through stimulation of CD4+ TH1 responses to mutated antigens, or neoantigens, selectively expressed by malignant tissue (168), and with the known synergistic effects of tumor specific CD4+ and CD8+ T cells, peptide epitopes capable of binding both MHC-I and MHC-II show potential to optimize vaccination efficiency (1, 207, 215).