Secretory IgA Dysfunction Underlies Poor Prognosis in Fusobacterium-Infected Colorectal Cancer

Authors

Ilseok Choi
Kyung-A Kim
Sang Cheol Kim
Donghwan Park
Ki Taek Nam
Jun Hyung Cha
Seungbyn Baek
Junha Cha
Hye-Yeong Jo
Minsun Jung
Melody Y Zeng
Irina Matei
Susan Bullman
Joong Bae Ahn
Yoon Dae Han
Han Sang Kim
Insuk Lee

Language

English

Publication Date

12-1-2025

Journal

Gut Microbes

DOI

10.1080/19490976.2025.2528428

PMID

40667611

PMCID

PMC12269704

PubMedCentral® Posted Date

7-16-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal role of Fn in impairing sIgA induction. We identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised mucosal immunity and increased bacterial infiltration. This IGAM signature effectively stratified Fn-positive patients, suggesting potential for targeted therapeutic approaches. Our findings reveal that Fn disrupts sIgA production, increasing tumor microbial burden and worsening prognosis through chronic inflammation in Fn-positive CRC.

Keywords

Colorectal Neoplasms, Animals, Immunoglobulin A, Secretory, Humans, Mice, Fusobacterium nucleatum, Fusobacterium Infections, Prognosis, Gastrointestinal Microbiome, Tumor Microenvironment, Female, Male, Tumor-Associated Macrophages, Mice, Inbred C57BL, Disease Models, Animal, Plasma Cells, Colorectal cancer, Fusobacterium nucleatum, secretory IgA, plasma cell development, tumor bacterial burden

Published Open-Access

yes

Recommended Citation

Choi, Ilseok; Kim, Kyung-A; Kim, Sang Cheol; et al., "Secretory IgA Dysfunction Underlies Poor Prognosis in Fusobacterium-Infected Colorectal Cancer" (2025). Faculty, Staff and Student Publications. 5392.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5392