Fusobacterium nucleatum promotes PD-L1 expression in cancer cells to evade CD8+ T cell killing in breast cancer

Background: A significant percentage of cancer-related fatalities are caused by breast Cancer (BC). Fusobacterium nucleatum (Fn) is a common Gram-negative anaerobic bacterium found in various inflammatory diseases, and there are also reports suggesting its involvement in Cancer progression. This study discussed molecular mechanisms of Fn-induced immune escape in BC cells.

Methods: mRNA and protein PD-L1 expression in BC cells were detected using qRT-PCR and western blot (WB). WB assayed NF-κB-related marker expressions (p-p65, p-65, p-p50, p-50) in cells. PD-L1 expression levels on the cell surface, Apoptosis and proliferation of CD8⁺ T and BC cells were measured via flow cytometry. ELISA tested TNFα, IFNγ, and granzyme B to assess the activation level of CD8⁺ T cells. The secretion level of LDH in the co-culture system was tested using an LDH detection kit to evaluate the cell death rate.

Results: BC cells stimulated by Fn can blunt tumor-killing of CD8⁺ T cells and their vitality. Fn treatment upregulates PD-L1 in BC cells. Rescue experiments using NF-κB inhibitors suggested that Fn treatment mediated NF-κB signaling and fostered PD-L1 expression in Cancer cells. Fn repressed the killing effect of CD8⁺ T cells on BC cells by triggering the NF-κB/PD-L1 signaling pathway.

Conclusion: Fn helps BC cells evade the killing effect of CD8⁺ T cells through the NF-κB/PD-L1 pathway.