Why CD4+ T cells matter in adoptive cell therapy for solid cancers

Cytotoxic CD8+ T cells have been the focus of research efforts to improve the efficacy of anticancer adoptive cell therapies. However, emerging evidence is highlighting the critical role of CD4+ T cells in these treatments, including chimeric antigen receptor-T cells. Although the presence of CD4+ T cells is known to be important for efficacy of cell therapies, the mechanisms by which CD4+ chimeric antigen receptor-T cells exert their beneficial effects remain incompletely understood. In this article, we review the roles of CD4+ T cells in adoptive cell therapy, highlighting understudied areas that are yet to be explored, and propose new directions to advance our understanding of their antitumour potential.