Esophageal squamous cell carcinoma derived sEV-PDL1 exhausts CD8T cells to promote immunosuppression.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy. Programmed death ligand 1 of small extracellular vesicles (sEV-PDL1) induce immune evasion and enhance tumor progression. However, the role of ESCC derived sEV-PDL1 in modulating CD8T cell remains unclear. sEVs were isolated through differential centrifugation. CD8T cells were isolated, stimulated and cultured with sEVs to evaluate the proportions, phenotypes, and functions by flow cytometry. Lentivirus infection and Crisper-Cas9 were used to constructed stable transgenic cell lines: Eca109-PDL1 and mEC25-PDL1. The proportions of CD8T cells in ESCC patients was lower than healthy donors (HD). Furthermore, a negative correlation between sEV-PDL1 and CD8T cell was observed. sEV-PDL1 induced CD8T cell exhaustion by reducing the expression levels of Ki67, Granzyme B (GrzmB), and interferon-γ (IFN-γ) both in vitro and in vivo. However, anti-PDL1 reversed the result. Our findings reveal that targeting sEV-PDL1 to rejuvenate CD8T cell functions is one of the mechnisms a promising therapeutic strategy for ESCC.