Patients with Increased Levels of Fusobacterium Tumoral Abundance are Associated with Better Outcomes in Mucinous Colorectal Cancer.

Abstract

There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives of this study were to assess the impact of Fusobacterium prevalence on immune cell expression and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumor microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with increased CD8 + lymphocyte (p = 0.018), regulatory T-cell (p = 0.001) and M2 macrophage (p = 0.001) expression. Similarly in the BRCC cohort, mucinous RC was associated with enhanced CD8 + lymphocyte (p = 0.022), regulatory T-cell (p = 0.047), and B-cell (p = 0.025) counts. Elevated Fusobacterium expression was associated with increased CD4+ (p = 0.031) and M1 macrophage (p = 0.006) expression, whilst M2 macrophages (p = 0.043) were under-expressed in the TCGA cohort. Increased Fusobacterium relative abundance in mucinous CRC was associated with improved clinical outcomes in our TCGA cohort despite having no association with MSI status (DSS: likelihood ratio p = 0.04, logrank p = 0.052). Fusobacterium abundance is associated with improved outcomes in mucinous CRC, possibly due its modulatory effect on the host immune response.