MMP11 promotes immune escape in esophageal carcinoma cells via the PD-L1/c-Myc signaling pathway.

[BACKGROUND] Esophageal cancer (ESCA) remains difficult to treat with surgery and chemotherapy showing limited impact on patient prognosis. Matrix metalloproteinase 11 (MMP11) has been linked to tumor progression and immune microenvironment modulation. This study explored MMP11's role in regulating the PD-L1/c-Myc pathway in ESCA.

[METHODS] MMP11 expression was analyzed in ESCA tissues and cell lines using real-time PCR and western blot. Kaplan-Meier survival curves assessed the relationship between MMP11 expression and patient survival. Functional assays, including wound healing and flow cytometry, were conducted to examine ESCA cell migration and apoptosis.

[RESULTS] MMP11 silencing reduced PD-L1 expression and inhibited cell migration, while promoting apoptosis. It also decreased the protein levels of c-Myc pathway-related proteins. Co-culturing MMP11-depleted ESCA cells with PBMCs altered T regulatory cell subsets and increased immunostimulatory cytokine levels. In vivo, MMP11 knockdown suppressed tumor growth, Ki-67 expression, and the PD-L1/c-Myc signaling pathway.

[CONCLUSION] These findings suggest that MMP11 activates the PD-L1/c-Myc pathway, contributing to immune evasion and ESCA progression. Targeting MMP11 could thus serve as a potential therapeutic approach for ESCA immunotherapy.