Fig. 4: Revised model of CD4 T cell licensing of cDC1s to induce CD8 T cell responses.

a In one model, CD4 T cells must be primed by cDC2s that have captured and presented tumor-derived antigens. These CD4 T cells migrate to the location of a cDC1 involved in priming CD8 T cells. b In a revised model, cDC1s serve as platforms for priming both CD4 T cells and CD8 T cells. The ligation of CD40 on the cDC1 surface during CD4 T cell priming is essential for strong licensing of cDC1s, and the lack of this ligation can lead to a failure in tumor rejection mediated by CD8 T cells. The mechanism downstream of CD40 signaling in cDC1s that leads to enhancement of CD8 responses is not currently known but may involve the induction of several costimulatory molecules, such as CD70 and 41BB, that augment the activation of CD8 T cells, as well as survival factors within the cDC1sthemselves.