Data from <i>Fusobacterium nucleatum</i> in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status

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<div>Abstract<p>The presence of <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) in colorectal carcinoma tissue has been associated with microsatellite instability (MSI), lower-level T-cell infiltrates, and poor clinical outcomes. Considering differences in the tumor–immune microenvironment between MSI-high and non–MSI-high carcinomas, we hypothesized that the association of <i>F. nucleatum</i> with immune response might differ by tumor MSI status. Using samples from 1,041 rectal and colon cancer patients within the Nurses’ Health Study and Health Professionals Follow-up Study, we measured <i>F. nucleatum</i> DNA in tumor tissue by a quantitative polymerase chain reaction assay. Multivariable logistic regression models were used to examine the association between <i>F. nucleatum</i> status and histopathologic lymphocytic reactions or density of CD3<sup>+</sup> cells, CD8<sup>+</sup> cells, CD45RO (PTPRC)<sup>+</sup> cells, or FOXP3<sup>+</sup> cells in strata of tumor MSI status. We adjusted for potential confounders, including CpG island methylator phenotype; LINE-1 methylation; and <i>KRAS, BRAF</i>, and <i>PIK3CA</i> mutations. The association of <i>F. nucleatum</i> with tumor-infiltrating lymphocytes (TIL) and intratumoral periglandular reaction differed by tumor MSI status (<i>P</i><sub>interaction</sub> = 0.002). The presence of <i>F. nucleatum</i> was negatively associated with TIL in MSI-high tumors [multivariable odds ratio (OR), 0.45; 95% confidence interval (CI), 0.22–0.92], but positively associated with TIL in non–MSI-high tumors (multivariable OR 1.91; 95% CI, 1.12–3.25). No significant differential association was observed for peritumoral lymphocytic reaction, Crohn-like lymphoid reaction, or T-cell densities. In conclusion, the association of <i>F. nucleatum</i> with immune response to colorectal carcinoma differs by tumor MSI status, suggesting that <i>F. nucleatum</i> and MSI status interact to affect antitumor immune reactions. <i>Cancer Immunol Res; 6(11); 1327–36. ©2018 AACR</i>.</p><p><i>See related Spotlight on p. 1290</i>.</p></div>