Exosomal O-GlcNAc transferase from esophageal carcinoma stem cell promotes cancer immunosuppression through up-regulation of PD-1 in CD8+ T cells

Esophageal carcinoma stem cells (ECSCs) are responsible for the initiation and therapy-resistance of esophageal cancer. Nutrient sensor O-GlcNAc transferase (OGT) promoted the growth and metastasis of cancer cells. However, the contributions of OGT to the tumorigenesis of ECSCs remain largely uncover. In the present study, as compared to matched non-stem cancer cells, the expression of OGT was higher in ALDH+ ECSCs. Knock down of OGT by lentivirus system reduced the self-renewal capacities and tumorigenicity of ALDH+ ECSCs. In addition, OGT in exosome derived from ALDH+ ECSCs was taken up by neighboring CD8+ T cells and increased the expression of PD-1 in CD8+ T cells. Down-regulation of OGT increased the apoptosis of ALDH+ ECSCs induced by CD8+ T cells, which could be blocked by overexpression of PD-1 in CD8+ T cells. Together, OGT in exosome from ECSCs protects ECSCs from CD8+ T cells through up-regulation of PD-1.