Activated fibroblasts induce immune escape of TSCC through CCL25 / AKT pathway

Abstract Objectives Accumulating evidence suggests that activated fibroblasts are the key cells in the T‐cell response to tumor immunosuppression. We attempted to investigate the effect of activated fibroblasts on PD‐L1 expression and the related immune escape mechanism in tongue squamous cell carcinoma. Methods Western blotting, qPCR, and other techniques were used to study the expression of PD‐L1 in tongue squamous cell carcinoma cells and the nude mouse model of transplanted tumors in vivo; clinical tissue samples were verified. In addition, we established a direct coculture model of T cells and tongue squamous cell carcinoma cells explore the mechanisms of immune escape. Results We found that PDGF‐BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD‐L1 expression. The activated fibroblasts inhibited T‐cell IFN‐γ secretion through the CCL25/Akt/PD‐L1 pathway, which indirectly inhibited T‐cell proliferation. Conclusion Activated fibroblasts can induce the high expression of PD‐L1 in the oral and tongue squamous cell carcinoma cell line Cal‐27 via the CCL25/CCR9/p‐Akt axis, to significantly inhibit the proliferation and IFN‐γ secretion of T cells and promote the immune escape of tongue squamous cell carcinoma cells.