Fusobacterium nucleatum Is Associated with Tumor Characteristics, Immune Microenvironment, and Survival in Appendiceal Cancer.

Emerging evidence highlights the role of the tumor microbiome, including Fusobacterium nucleatum (Fn), in a wide range of gastrointestinal cancers. Fn purportedly contributes to tumorigenesis by activating oncogenic pathways and modulating immune responses. Although the prevalence and impact of Fn has been extensively studied in colorectal cancer, no previous systematic or in situ studies have been performed in appendiceal cancer (AC). The aim of this study was to evaluate the prevalence and association of Fn density in AC with clinical factors and oncologic outcomes. Archival tissue from 54 patients with AC was assessed for Fn density using RNA in situ hybridization. Clinicopathological variables were obtained for each case through electronic medical record review, and the immune microenvironment was characterized in each case using immunohistochemistry to quantify CD3+ and CD8+ T lymphocytes and M1-/M2-like tumor-associated macrophages. In AC, Fn density was associated with patient age, tumor grade, and histologic subtype. Fn was negatively associated with CD3+ and CD8+ T lymphocytes and positively associated with M2-like TAMs in low-grade AC. Interestingly, tumor Fn content was associated with better overall and progression-free survival, even when controlling for tumor grade. In this exploratory study, we found that Fn is prevalent in AC. Fn is associated with a number of clinical, pathologic, immunologic, and prognostic variables in AC that are distinct from the corresponding observed associations in colorectal cancer. Further research is warranted to validate these findings and explore the mechanistic contributions of Fn to AC pathogenesis or immune response.