Fusobacterium nucleatum and T-cells in Colorectal Carcinoma

By K. Mima, Y. Sukawa, Reiko Nishihara, Z. Qian, Mai Yamauchi, K. Inamura, S. Kim, A. Masuda, J. Nowak, K. Nosho and 15 more. JAMA Oncology, 2015

618 citations recorded by the source corpus.

Importance Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by down-regulating antitumor T-cell-mediated adaptive immunity. Objective To test the hypothesis that higher amount of Fusobacterium nucleatum in colorectal carcinoma tissue is associated with lower density of T-cells in tumor tissue. Design A cross-sectional analysis was conducted on colorectal carcinoma cases in two U.S. nationwide prospective cohort studies. The amount of Fusobacterium nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high versus low). Multivariable ordinal logistic regression analysis was conducted to assess associations of the amount of Fusobacterium nucleatum with densities (quartiles) of T-cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted two-sided α level to 0.013 for multiple hypothesis testing. Setting The Nurses’ Health Study and the Health Professionals Follow-up Study. Participants 598 colon and rectal carcinoma cases. Main outcomes and measures Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ T-cells in tumor tissue, determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Results Fusobacterium nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with Fusobacterium nucleatum-negative cases, Fusobacterium nucleatum-high cases were inversely associated with the density of CD3+ T-cells (for a unit increase in quartile categories of CD3+ T-cells as an outcome: multivariable odds ratio, 0.47; 95% confidence interval, 0.26 to 0.87; Ptrend = 0.006). The amount of Fusobacterium nucleatum was not significantly associated with the density of CD8+, CD45RO+, or FOXP3+ T-cells (Ptrend > 0.013). Conclusions and relevance The amount of tissue Fusobacterium nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue. Upon validation, our human population data may provide an impetus for further investigations on potential interactive roles of Fusobacterium and host immunity in carcinogenesis.

Subfields: Biotechnology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/40ed920d62d1386dff7e31addc864586d5c86ae6

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Citations in the corpus

The microbiome and cancer (2018, result): “Consistent with the findings in mouse models, Fusobacterium is associated with an inflammatory microenvironment in human samples: increased Fusobacterium carriage in tumour tissue is associated with increased levels of NF-κB transcripts [46,52] and decreased CD3-positive T-cell loads, as well as a w”
The microbiome and human cancer (2021, background): “Immunologically, intratumor microbes often create tolerogenic programming through pattern recognition receptor (PRR) ligation with lower proportions of TILs, including CD8 T cells, and occasionally more CD4CD25FoxP3 Tregs, as observed in colorectal, pancreatic, breast, and lung cancers (18, 23, 34, ”
Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc (2016, background): “Increased levels of F. nucleatum correlate with specific molecular subsets of CRCs such as the CpG island methylator phenotype and microsatellite instability (Mima et al., 2015; Tahara et al., 2014).”
Natural history of the infant gut microbiome and impact of antibiotic treatments on strain-level diversity and stability (2015, background): “These studies have largely focused on characterizing healthy adults (1) and finding commonalities among patients suffering from diseases such as inflammatory bowel disease (2, 3), type 2 diabetes (4), obesity (5–9), metabolic disorders (10–15), colorectal cancer (16, 17), liver cirrhosis (18, 19), r”
Interaction between microbiota and immunity in health and disease (2020, background): “nucleatum in human colorectal cancer tissue are furthermore associated with a lower density of CD3 T cells, a population associated with a more favorable clinical outcome.(188) In remote tissues such as the liver, the intestinal commensal Clostridium species utilize bile acids as messengers to enhan”