Abstract
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 CD8+T cell remains unclear. sEVs were isolated through differential centrifugation. CD8+T 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-PDL1kd and mEC25-PDL1ko. The proportions of CD8+T cells in ESCC patients was lower than healthy donors (HD). Furthermore, a negative correlation between sEV-PDL1 and CD8+T cell was observed. sEV-PDL1 induced CD8+T 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 CD8+T cell functions is one of the mechnisms a promising therapeutic strategy for ESCC.
Published Version
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