To date, immune check-point inhibitors (ICIs), particularly inhibitors of programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) have become prominent in cancer treatment and also improved life expectancy of cancer patients. As key regulators of PD-1/PD-L1 axis, the recruitment of tumor-associated macrophages (TAMs) enhances aggressive and invasive properties of tumors in immunosuppressive tumor microenvironment (TME) and promotes epithelial-mesenchymal transition (EMT). The aims of the study were first to characterize the critical links among PD-L1, TME and EMT process and, further, to explore the sensitivity of different chemical agents to different PD-L1 expression groups. Bioinformatical analysis revealed that PD-L1 was highly expressed in OSCC and higher PD-L1 expression correlated with worse survival in patients. Notably, PD-L1 was positively correlated with macrophages infiltration and EMT markers gene expression. Moreover, patients in the PD-L1high group were at a significant chance of benefiting from ICI treatment and they also showed higher sensitivity to the chemical drugs (olaparib, paclitaxel, docetaxel, and pazopanib). These findings implicate PD-L1 could serve as a novel target for prognostic and therapeutic approaches in OSCC patients; PD-L1-mediated immune evasion might be attributable to the infiltration of macrophages, resulting EMT progress; Chemical agents in combination with PD-L1 inhibitor could be served as personalized treatment plan for OSCC patients so as to maximize patient benefit.

This study investigated the effect of Corydalis saxicola Bunting total alkaloids (CSBTA) on pyroptosis in macrophages (Mϕ). In the Mϕ pyroptosis model, an inverted fluorescence microscope was used to assess cell pyroptosis, while a scanning electron microscope was used to observe morphological changes in Mϕ. NLR family pyrin domain‐containing 3 (NLRP3), caspase‐1, and gasdermin D (GSDMD) expression levels were detected by polymerase chain reaction and western blotting, whereas interleukin‐1 (IL‐1) and interleukin‐18 (IL‐18) expression levels were measured by an enzyme‐linked immunosorbent assay. After pretreatment with CSBTA or the caspase‐1 inhibitor, acetyl‐tyrosyl‐valyl‐alanyl‐aspartyl‐chloromethylketone (Ac‐YVAD‐cmk), it was discovered that NLRP3, caspase‐1, and GSDMD expressions were significantly reduced at both the mRNA and protein levels, as were IL‐1 and IL‐18 levels. The inhibitory effects of CSBTA and Ac‐YVAD‐cmk did not differ significantly. These findings indicate that CSBTA blocks Porphyromonas gingivalis‐lipopolysaccharide‐induced Mϕ pyroptosis.

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