Potential role of intratumoral Fusobacterium nucleatum and interleukin-1 beta in breast cancer cell growth

Background: It has been shown that the human breast harbors a rich and diverse microbiome, with significant differences observed between tumor tissue and normal breast tissue. Recently, Fusobacterium nucleatum (F. nucleatum) has been shown to affect breast cancer growth, but the underlying mechanism remains enigmatic. Methods: Breast cancer tissues were obtained from clinical patients and analyzed for the microbiome composition using 16S rDNA sequencing and qPCR. Both serum and intratumoral cytokine levels were measured to assess their correlation with intratumoral F. nucleatum. Breast cancer cell lines and patient-derived cancer cells were infected with different strains of F. nucleatum, followed by different analyses. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals to investigate the immunoregulatory effect of F. nucleatum. Results: Our results identified a higher abundance of F. nucleatum in breast cancer tissue compared to adjacent normal breast tissue, which strongly correlated with intratumoral IL-1β levels. In vitro studies confirmed this correlation, demonstrating that infection of breast cancer cells with F. nucleatum promotes tumor growth. Further investigation suggested that F. nucleatum induces IL-1β secretion in both breast cancer cells and PBMCs, but only IL-1β secreted by breast cancer cells stimulates cancer cell growth. Inhibition of NLRP3 reversed the growth-promoting effect of F. nucleatum on breast cancer cells. Conclusion: Our results demonstrate the role of F. nucleatum in stimulating breast cancer cell growth. Therefore, targeting intratumoral F. nucleatum could provide a promising therapeutic approach to combat breast cancer.