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

Abstract

ObjectivesAccumulating 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.MethodsWestern 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.ResultsWe 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.ConclusionActivated 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.

Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning

“…Through GSVA, we found that the genes in the high‐risk group were enriched mainly in angiogenesis, stromal cells, M2 macrophages, the extracellular matrix (ECM) and glucose metabolism. Stromal cells and M2 macrophages can achieve immunosuppression and immune escape through various mechanisms 39–41 . Elevated glucose metabolism promotes the proliferation of BC cells and induces BC recurrence and metastasis 42,43 .…”

“…Stromal cells and M2 macrophages can achieve immunosuppression and immune escape through various mechanisms. [39][40][41] Elevated glucose metabolism promotes the proliferation of BC cells and induces BC recurrence and metastasis. 42,43 Dysregulation of the ECM can disrupt tissue homeostasis, which can facilitate the occurrence and progression of tumours.…”