Further, since the presence of a CD4+ T cell epitope is required for an effective anti-tumor CD8+ T cell response, it remains to be determined how added CD4+ T cell helper epitopes dually control Tprec/prog and Tex-int programming beyond intrinsic CD8+ T cell TCR signaling by low avidity epitopes at the site of the APC. This evidence concerns the gene CD4 and neoplasm.