Pulmonary colonization of Candida albicans drives breast cancer lung metastasis via candidalysin
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.
Authors
- Peng Tang (ORCID: https://orcid.org/0000-0002-5403-0817)
- Changbin Chen (ORCID: https://orcid.org/0000-0002-7961-3488)
- Ming Guan (ORCID: https://orcid.org/0000-0002-8861-1281)
- Zhongyi Ma (ORCID: https://orcid.org/0000-0002-4532-1890)
- Linqi Wang (ORCID: https://orcid.org/0000-0002-5243-341X)
- Lin Zhu (ORCID: https://orcid.org/0000-0002-2801-3626)
- Feiyan Gao
- Mengdi Ren (ORCID: https://orcid.org/0000-0002-0028-3501)
- Yuping Zhang (ORCID: https://orcid.org/0000-0001-9105-6621)
- Xinlin Yang
- Jin Wu (ORCID: https://orcid.org/0009-0007-4407-4959)
- Hongdan Chen
- Yulan Liu
- Yueru Tian
- Yike Fang
- Chong Li
- Lei Chen
- Lihan Liu
- Yumei Wang
Institutions
- Shanghai Medical College of Fudan University (CN)
- Hong Kong Baptist University (HK)
- Southwest University (CN)
- Army Medical University (CN)
- Chongqing University (CN)
- Chinese Academy of Sciences (CN)
- Chengdu Medical College (CN)
- Fudan University (CN)
- Shanghai Institute of Materia Medica (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Southwest Hospital (CN)
- Institute of Microbiology (CN)
- Chongqing Cancer Hospital (CN)
- Huashan Hospital (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-10-28
- DOI
- https://doi.org/10.64898/2026.10.23.759946
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- preprint
Funders
- National Natural Science Foundation of China
- Southern Medical University