Fig. 2.

Potential strategies to improve the efficacy of PD-1-targeted immunotherapy. Three key factors that should be manipulated to enhance the efficacy of PD-1 blockade are (1) number, (2) effector function and (3) durability. To manipulate these factors, four potential strategies are proposed. (A and B) Increase in the quantity (A) and/or improve the proliferative capacity (B) of the stem-like T-cell subset before PD-1 therapy. These should result in the generation of a higher number of transitory CD8 T cells after PD-1 blockade. (C) Accelerating the differentiation of stem-like T cells into transitory T cells during PD-1 blockade. This may be achieved by combination therapy and induces more transitory T cells with enhanced effector function. (D) Inhibiting differentiation from transitory T cells into terminally exhausted T cells during and/or after PD-1 therapy. This approach will prolong the durability of transitory T cells. Created with BioRender.com.