Pulmonary colonization of Candida albicans drives breast cancer lung metastasis via candidalysin
- 1School of Pharmaceutical Sciences, Southern Medical University
Abstract
The intratumoral mycobiome is emerging as a key modulator of cancer progression, with specific fungal taxa as potential biomarkers. However, whether and how mycobiomes colonizing distant organs contribute to tumor evolution remains largely unexplored. Here, we identify selective enrichment of Candida albicans in breast cancer lung metastases. Mechanistically, the fungal virulence factor candidalysin activates pulmonary mast cells, which release chemotactic mediators that expand immunosuppressive populations and suppress cytotoxic lymphocyte activity, remodeling the lung into a metastasis-permissive microenvironment. Analysis of clinical isolates and isogenic mutants further demonstrates that candidalysin secretion levels dictate metastasis-promoting potential. Informed by these findings, we developed a combination regimen that concurrently eliminates fungal colonization, stabilizes mast cells, and reverses the immunosuppressive microenvironment, thereby significantly curtailing metastatic progression. Collectively, our study establishes pulmonary C. albicans colonization as a driver of breast cancer lung metastasis and provides a mechanistic framework for targeting mycobiome-host interactions in metastatic disease.
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BibTeX
@misc{ma2026pulmonary,
title = {{Pulmonary colonization of Candida albicans drives breast cancer lung metastasis via candidalysin}},
author = {Z. Ma and L. Chen and Y. Fang and F. Gao and L. Liu and J. Wu and H. Chen and Y. Tian and Y. Zhang and X. Yang and Y. Wang and M. Ren and Y. Liu and L. Zhu and C. Chen and M. Guan and P. Tang and L. Wang and C. Li},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.23.759946},
url = {https://www.biorxiv.org/content/10.64898/2026.10.23.759946v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Pulmonary colonization of Candida albicans drives breast cancer lung metastasis via candidalysin
AU - Z. Ma
AU - L. Chen
AU - Y. Fang
AU - F. Gao
AU - L. Liu
AU - J. Wu
AU - H. Chen
AU - Y. Tian
AU - Y. Zhang
AU - X. Yang
AU - Y. Wang
AU - M. Ren
AU - Y. Liu
AU - L. Zhu
AU - C. Chen
AU - M. Guan
AU - P. Tang
AU - L. Wang
AU - C. Li
PY - 2026
DA - 2026/10/23
PB - bioRxiv
DO - 10.64898/2026.10.23.759946
UR - https://www.biorxiv.org/content/10.64898/2026.10.23.759946v1
AB - The intratumoral mycobiome is emerging as a key modulator of cancer progression, with specific fungal taxa as potential biomarkers. However, whether and how mycobiomes colonizing distant organs contribute to tumor evolution remains largely unexplored. Here, we identify selective enrichment of Candida albicans in breast cancer lung metastases. Mechanistically, the fungal virulence factor candidalysin activates pulmonary mast cells, which release chemotactic mediators that expand immunosuppressive populations and suppress cytotoxic lymphocyte activity, remodeling the lung into a metastasis-permissive microenvironment. Analysis of clinical isolates and isogenic mutants further demonstrates that candidalysin secretion levels dictate metastasis-promoting potential. Informed by these findings, we developed a combination regimen that concurrently eliminates fungal colonization, stabilizes mast cells, and reverses the immunosuppressive microenvironment, thereby significantly curtailing metastatic progression. Collectively, our study establishes pulmonary C. albicans colonization as a driver of breast cancer lung metastasis and provides a mechanistic framework for targeting mycobiome-host interactions in metastatic disease.
ER -