Gastric cancer-derived nanovesicles affect the viability and effector function of an NK cell line

Objective(s): Gastric cancer is characterized by high mortality rates due to its aggressive progression and immune-evasion strategies. Tumor-derived exosomes (TDEs) are nanovesicles mainly known for their role in modulating the tumor microenvironment, including the suppression of immune effector cells such as NK cells. Materials and Methods: This study aimed to assess the impact of exosomes released from the human AGS GC cell line on the viability and effector function of the NK-۹۲ cell line. Exosomes were characterized using FE-SEM, DLS, and flow cytometry, confirming their size (approximately ۱۰۹ nm) and expression of the CD۶۳ marker. Results: Co-culture of NK-۹۲ cells with exosomes at ۳۰ µg/ml for ۴۸ hours revealed a significant reduction in cell viability in the MTT assay. Quantitative real-time PCR showed increased expression of suppression markers (NKG۲A, TGF-β۱, and LAG-۳), while ELISA indicated decreased IFN-γ production. Flow cytometry-based cell cycle analysis demonstrated increases in the sub-G۱ (apoptotic) and G۰/G۱ phases. Conclusion: These results suggest that GC-derived exosomes may impair NK cells, potentially contributing to immune evasion and tumor progression. However, these findings were obtained using immortalized AGS and NK-۹۲ cell lines and require validation in primary cells and in vivo models. Insights from this study could inform novel immunotherapeutic approaches targeting exosomal pathways in GC.

کلیدواژه ها:

Gastric cancer ، Tumor-derived exosomes ، Natural killer cells ، Immune evasion ، Cytotoxicity