Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer

Fusobacterium nucleatum ( F. nucleatum) is enriched in colorectal cancer (CRC) tissues and a high amount of F. nucleatum was associated with an immunosuppressive tumor environment. PD-L1 is an important immune checkpoint expressed on tumor cells and promotes tumor immune escape. Whether PD-L1 is regulated by F. nucleatum is still unclear. We demonstrated that F. nucleatum promoted CRC progression and upregulated PD-L1 protein expression in CRC cell lines. Combined m(6)A-seq and RNA-seq identified m(6)A-modified IFIT1 mediating F. nucleatum induced PD-L1 upregulation. IFIT1 mRNA was modified with m6A modifications in 3'UTR and the m(6)A levels were altered by F. nucleatum treatment. Our results also indicated that IFIT1 served as a potential oncogene in CRC and regulated PD-L1 protein levels through altering PD-L1 ubiquitination. Clinical CRC data confirmed the correlation among F. nucleatum abundance, IFIT1 and PD-L1 expressions. Our work highlighted the function of F. nucleatum in stimulating PD-L1 expression through m(6)A-modified IFIT1 and provided new aspects for understanding F. nucleatum mediated immune escape.

Automated summary

This study reveals that Fusobacterium nucleatum (F. nucleatum) is enriched in colorectal cancer (CRC) tissues and is associated with an immunosuppressive tumor environment. The researchers demonstrate that F. nucleatum promotes CRC progression by upregulating PD-L1 protein expression through the m(6)A-modified IFIT1 pathway. Clinical data confirms the correlation between F. nucleatum abundance, IFIT1, and PD-L1 expressions.