Differential immune microenvironmental features of microsatellite-unstable colorectal cancers according toFusobacterium nucleatumstatus

It has been suggested thatFusobacterium nucleatum(Fn) may differentially impact tumor immune responses according to microsatellite instability (MSI) status in colorectal cancers (CRCs). We aimed to reveal the detailed relationship between intratumoralFnand immune microenvironmental features in MSI-high CRCs. A total of 126 MSI-high CRCs were subjected to analyses for intratumoralFnDNA load using quantitative PCR and for densities of tumor-infiltrating immune cells, including CD3(+)T cells, CD4(+)T cells, CD8(+)T cells, FoxP3(+)T cells, CD68(+)macrophages, CD163(+)macrophages, and CD177(+)neutrophils, at invasive margin (IM) and center of tumor (CT) areas using computational image analysis of immunohistochemistry. Based on theFnload, the 126 MSI-high CRCs were classified intoFn-high, -low, and -negative subgroups. TheFn-high subset of MSI-high CRCs was significantly correlated with larger tumor size and advanced invasion depth (p = 0.017 andp = 0.034, respectively). Compared with theFn-low/negative subgroup,Fn-high tumors demonstrated significantly lower density of FoxP3(+)cells in both IM and CT areas (p = 0.002 andp = 0.003, respectively). Additionally,Fn-high was significantly associated with elevated CD163(+)cell to CD68(+)cell ratio in only CT areas of MSI-high CRCs (p = 0.028). In conclusion, theFn-enriched subset of MSI-high CRCs is characterized by increased tumor growth and invasion and distinct immune microenvironmental features, including decreased FoxP3(+)T cells throughout the tumor and increased proportion of M2-polarized macrophages in the tumor center. These findings collectively support thatFnmay be linked to pro-tumoral immune responses in MSI-high CRCs.

Automated summary

The study found that in MSI-high CRCs, tumors with high levels of Fn were correlated with larger size and more advanced invasion depth. Fn-high tumors showed lower density of FoxP3(+) cells throughout the tumor and an increased ratio of CD163(+)cells to CD68(+)cells in the CT area of MSI-high CRCs.