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Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8 + T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8 + labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8 + labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8 + was also significantly associated with the microbiota composition in the tumor: CD8 + T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8 + T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8 + T cells and directly associated with CC recurrence. The link between this microbe, CD8 + T cells, and DFS has not been previously shown.

oncotarget

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial