The role of CD4 T cells in rejection of solid tumors

The focus in cancer immunotherapy has mainly been on CD8 T cells, as they can directly recognize cancer cells. CD4 T cells have largely been neglected, because most cancers lack MHC II expression and cannot directly be recognized by CD4 T cells. Yet, tumor antigens can be captured and cross-presented by MHC II-expressing tumor stromal cells. Recent data suggest that CD4 T cells act as a swiss army knife against tumors. They can kill cancer cells, if they express MHC II, induce tumoricidal macrophages, induces cellular senescence of cancer cells, destroy the tumor vasculature through cytokine release and help CD8 T cells in the effector phase. We foresee a great future for CD4 T cells in the clinic, grafted with tumor antigen specificity by T cell receptor gene transfer, either alone or in combination with engineered CD8 T cells.