Reciprocal interactions between the gut microbiome and mammary tissue mast cells promote metastatic dissemination of HR+ breast tumors

Feng T, Azar F, Buchta Rosen C, McGinty M, Putelo A, Koli S, Marino N, German R, Podicheti R, Dreger S, Fowler W, Greenfield S, Robinson S, Rutkowski . (2022)

Cancer Immunology Research

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, prior to breast tumor initiation enhances early dissemination of hormone-receptor positive (HR⁺) mammary tumor cells. Here, we sought to define mammary tissue mediators of dysbiosis-induced tumor dissemination. Using multiple methods, we identified that the commensal dysbiosis induced abundance and profibrogenicity of mast cells in the mammary tissues, while the phenotypes remaining skewed after tumor implantation. Fibroblast activation and tissue remodeling are associated with enhanced breast tumor metastasis. By integrating pharmacological approaches and adoptive transfer, we confirmed that the mammary tissue mast cells from dysbiotic animal aggravates the dissemination of HR⁺ tumor cells. Collagen levels in mammary tissues from HR⁺ breast cancer patients also correlated with mast cell abundance, suggesting mast cell-mediated fibroblast activation is clinically relevant. Together, these data demonstrate that dysbiosis-induced profibrogenicity in mast cells in mammary tissues orchestrate early dissemination of HR⁺ breast tumors.

Cancer Immunology Research

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