Longchai Jiangxue Prescription Inhibited Lung Cancer Immune Escape by Regulating Immune Checkpoint PD-L1

Background: Not all lung cancer patients respond well to immune checkpoint inhibitors targeting PD-L1/PD-1, and resistance to PD-L1/PD-1 inhibitors significantly limit their clinical application and therapeutic efficacy. Longchai Jiangxue Fang (LC) is a traditional Chinese medicine compound that has shown potential and effectiveness in the treatment of myeloproliferative neoplasms. However, the effects and potential underlying mechanisms of LC against lung cancer remain unclear. Methods: A co-culture model of T cells with lung cancer cells was established. Cancer cell growth was measured by colony formation. T cell activation was detected by ELISA of inflammatory cytokines and flow cytometry of CD8+GzmB+ T cells. PD-L1 expression was detected by western blot. In vivo growth was measured using a mouse xenograft tumor model. Immunohistochemistry analysis was performed to determine T cells activation in tumor tissues. The potential targets of LC in lung cancer were predicted by network pharmacology. The AKT signaling was detected using in T cell-cancer cell co-culture model.Results: LC treatment promoted immune activation of T cells and the toxicity to lung cancer cells in vitro and in vivo. Network pharmacology revealed the PI3K-AKT as the most abundant signaling pathway in lung cancer cells under LC treatment. Cellular experiments confirmed that the phosphorylation of PI3K and AKT was repressed by LC treatment in both A549 cells and H1299 cells. LC treatment could abolish the immune evasion of lung cancer cells induced by Akt activator. Conclusion: Our findings presented LC as a promising therapeutic agent for lung cancer and identified the involvement of AKT signaling in the function of LC.