A few possibilities might explain this discrepancy: 1) IL-21 in the setting of IT and anti-tumor responses bypasses the need for CD4+ help; 2) the effects of our highly stimulatory IT are such that they “rescue” the “helpless” CD8+ cells from exhaustion; or 3) the regulation of bystander activated memory CD8+ T-cells is different than the regulation of antigen specific CD8+ T-cells. This evidence concerns the gene CD8A and neoplasm.