Qingre Lidan decoction suppresses cholangiocarcinoma progression and enhances CD8+ T cell-mediated immunity by targeting the STAT3/NF-κB/PD-L1 axis

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Background : Cholangiocarcinoma (CCA) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Qingre Lidan Decoction (QRLD), a traditional Chinese medicine formula, has been widely used for treating hepatobiliary diseases. However, its anti-tumor efficacy and underlying mechanisms in CCA remain largely unknown. Methods: The therapeutic effects and molecular mechanisms of QRLD in CCA were investigated using a combination of network pharmacology analysis, in vitro experiments with human CCA cell lines, and in vivo studies in a mouse xenograft model. Key pathways and core targets were identified through bioinformatics. Results: Network pharmacology analysis identified 148 potential targets of QRLD in CCA, with core targets involved in cancer progression and immune regulation, such as AKT1, TP53, and TNF. Both in vitro and in vivo experiments demonstrated that QRLD significantly inhibited CCA cell proliferation and tumor growth. Mechanistic studies revealed that QRLD exerted its anti-tumor effects primarily by inducing apoptosis and inhibiting migration. Importantly, QRLD suppressed PD-L1 expression in CCA cells via downregulation of the STAT3 and NF-κB signaling pathways, and enhanced CD8 + T cell activation, chemotaxis, and cytotoxicity against CCA cells. Conclusions: This study provides evidence that Qingre Lidan Decoction suppresses cholangiocarcinoma progression. The anti-tumor and immunomodulatory effects are mediated through multi-target actions, including suppression of PD-L1 expression via the STAT3/NF-κB axis and enhancement of CD8 + T cell-mediated anti-tumor immunity. These findings support the potential of QRLD as a novel therapeutic strategy for CCA and warrant further clinical investigation.

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