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• W4315705026 abstract "Accumulating evidence shows that PD-L1 expression on dendritic cells (DC) is critical for cancer immunotherapy and that Porphyromonas gingivalis (Pg) colonization aggravates the progression of upper gastrointestinal cancers. However, the effects of Pg infection on PD-L1 expression on DCs and related immune consequences in the infection milieu of oral cancer remain unexplored. Here, we found that Pg infection robustly enhanced PD-L1 expression on DCs in a gingipain-dependent manner in cultured cell and systemic infection assays. Pg infection suppressed antigen-specific CD8+ T cells through upregulation of PD-L1 expression on ovalbumin (OVA)-pulsed DCs. This suppression was manifested by decreased IFNγ, perforin, granzyme B, and CD107a. Further analysis showed that Pg drastically reduced CD8+ T cells' ability to lyse OVA-pulsed target cells. Additionally, Pg infection increased the phosphorylation of Akt and STAT3, leading to a significant increase in PD-L1 expression. This was substantiated by using siRNA, overexpression plasmids, and pharmacologic inhibitors. Consistent with the in vitro observations, in a syngeneic mouse oral cancer model, Pg infection significantly enhanced PD-L1 expression on DCs from intratumoral tissues and cervical lymph nodes and exacerbated oral cancer progression, whereas a Pg lysine-specific, gingipain-defective mutant failed to do so. These influences of Pg were largely diminished when tumor cells were pretreated with antibiotics or a STAT3 inhibitor. Therefore, we demonstrated that Pg infection upregulates PD-L1 expression on DCs through Akt-STAT3 signaling, suppresses CD8+ T-cell cytotoxicity, and aggravates oral cancer growth, suggesting targeting Pg, and/or its mediated signaling, could be a therapeutic strategy to improve the efficacy of checkpoint blockade immunotherapy." @default.
• W4315705026 created "2023-01-12" @default.
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• W4315705026 date "2023-01-12" @default.
• W4315705026 modified "2023-10-05" @default.
• W4315705026 title "<i>P. gingivalis</i>Infection Upregulates PD-L1 Expression on Dendritic Cells, Suppresses CD8+ T-cell Responses, and Aggravates Oral Cancer" @default.
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• W4315705026 doi "https://doi.org/10.1158/2326-6066.cir-22-0541" @default.
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