Fusobacterium nucleatum Promotes Exosomal LncRNA MANCR Secretion from Colorectal Cancer Cells to Induce PD-L1 Expression in Macrophages - PubMed
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- #Fusobacterium nucleatum
- #Exosomal lncRNA
- #PD-L1 upregulation
- Fusobacterium nucleatum (F. nucleatum) promotes colorectal cancer (CRC) progression and correlates with poor prognosis in patients.
- F. nucleatum activates NF-κB signaling in CRC cells, inducing the transcription of long non-coding RNA MANCR.
- MANCR is packaged into exosomes via the ESCRT-III/Alix complex and transferred to tumor-associated macrophages.
- In macrophages, exosomal MANCR interacts with hnRNP U to stabilize PD-L1 mRNA, leading to sustained PD-L1 surface expression.
- High F. nucleatum levels are associated with PD-L1 upregulation in macrophages, reduced CD8+ T-cell cytotoxicity, and suppressed antitumor immunity.
- In humanized mouse models, F. nucleatum exposure inhibits CD8+ T-cell infiltration and granzyme B activity, facilitating tumor growth and metastasis.
- Targeting the F. nucleatum/MANCR/PD-L1 axis may offer a strategy to overcome immune resistance in colorectal cancer.