More importantly, we observed that PD-L1/PD-1 signaling mainly affected the metabolic profile of donor T cells in GVHD target tissues but not in the spleen, and a synergism between tissue-specific PD-L1/PD-1 signaling and STAT3 deficiency in donor T cells contributed to prevention of GVHD. Here, STAT3 is linked to graft versus host disease.