CXCL11 secreted by cancer-associated fibroblasts promotes nasopharyngeal carcinoma progression via CXCR3/PD-L1 axis

The secretion of chemokines by cancer-associated fibroblasts (CAFs) is a critical driver of cancer progression. Nevertheless, the precise contribution of CAFs in the nasopharyngeal carcinoma (NPC) tumor microenvironment to disease progression is yet to be fully understood. In this study, C-X-C motif chemokine ligand 11 (CXCL11) was identified to be upregulated in tumor tissues of NPC patients and NPC cells compared to counterpart normal tissues and cell lines. The CAFs-secreted CXCL11 was found to enhance the proliferative, invasive, and migratory capacities of NPC cells. CAFs-derived CXCL11 upregulates CXCR3 expression to facilitate NPC cell proliferation, migration, and invasion. Through mechanism investigation, we confirmed that CXCL11/CXCR3 axis upregulated PD-L1 expression through p65-mediated transcription activation. Finally, in vivo experiments further validated the tumor-promoting role of CAFs-secreted CXCL11 in NPC. In conclusion, our findings reveal a novel mechanism wherein CAFs-secreted CXCL11 promotes NPC malignant progression by activating the CXCR3/PD-L1 signaling axis.