Commensal Nakaseomyces glabratus migrates into prostate tumors to accelerate cancer progression
Abstract Recent studies demonstrate that the gut mycobiota plays a key role in several tumors. However, the contribution of commensal fungi to prostate cancer initiation and progression remains understudied. Here we find that Nakaseomyces glabratus is enriched in fecal, blood and tumor samples of patients with castration-resistant prostate cancer, correlating with patients’ poor overall survival. Oral administration of N. glabratus to castrated mice accelerated cancer progression by promoting infiltration and activation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, androgen deprivation therapy increases intestinal permeability, resulting in the leakage of N. glabratus from the gut to the tumor site, activating PMN-MDSCs via the Dectin-2 receptor. Treatment of mice with a negatively charged intestinal hydrogel blocks N. glabratus translocation to tumor, reducing PMN-MDSCs’ intratumoral infiltration and activation. Taken together, these findings reveal that the gut-to-tumor translocation of N. glabratus contributes to endocrine resistance in prostate cancer by enhancing the immunosuppressive microenvironment of these tumors.
Authors
- Simone Mosole (ORCID: https://orcid.org/0000-0002-0765-1426)
- Alessandra De Giani (ORCID: https://orcid.org/0000-0002-4053-8345)
- Pedron Serena
- Pasquale Rescigno (ORCID: https://orcid.org/0000-0002-4668-4765)
- Martina Troiani
- Matteo Brunelli (ORCID: https://orcid.org/0000-0002-5023-3780)
- Emiliano Pasquini (ORCID: https://orcid.org/0000-0001-9158-9671)
- Luisa Maraccani (ORCID: https://orcid.org/0000-0002-3195-2720)
- Nicolò Bancaro (ORCID: https://orcid.org/0000-0003-2102-6421)
- Tanja Rezzonico Jost
- Isabella Giacomini (ORCID: https://orcid.org/0000-0002-7154-7930)
- Martino Pedrani (ORCID: https://orcid.org/0000-0002-8502-8226)
- Nicolò Pernigoni (ORCID: https://orcid.org/0000-0001-5115-8447)
- Ricardo Pereira Mestre (ORCID: https://orcid.org/0000-0002-3123-3697)
- Andrea Rinaldi (ORCID: https://orcid.org/0000-0003-3234-0563)
- Yingxi Du
- Christian Jobin (ORCID: https://orcid.org/0000-0002-3733-1001)
- Aurora Valdata (ORCID: https://orcid.org/0000-0002-9293-5502)
- Giovanna Pecoraro (ORCID: https://orcid.org/0009-0003-6743-6933)
- Giuseppe Attanasio
- Wei Yuan (ORCID: https://orcid.org/0000-0001-8004-1846)
- Lewis Gallagher (ORCID: https://orcid.org/0000-0003-2694-3157)
- Alessandro Morlacco (ORCID: https://orcid.org/0000-0003-0201-0758)
- Penny Flohr (ORCID: https://orcid.org/0000-0001-9908-0474)
- Raad Z. Gharaibeh (ORCID: https://orcid.org/0000-0001-5484-8902)
- Johann S. de Bono (ORCID: https://orcid.org/0000-0002-2034-595X)
- Daniele Braga (ORCID: https://orcid.org/0000-0003-2168-8425)
- Andrea Alimonti (ORCID: https://orcid.org/0000-0002-9362-2313)
- Giuseppe Reitano (ORCID: https://orcid.org/0009-0007-8021-9879)
- Monica Montopoli (ORCID: https://orcid.org/0000-0001-6182-4132)
- Martino Maddalena (ORCID: https://orcid.org/0000-0003-4740-3096)
- Yuxin Li (ORCID: https://orcid.org/0000-0001-9739-9860)
- Lei Liu (ORCID: https://orcid.org/0000-0002-9995-9080)
- Ping Lai (ORCID: https://orcid.org/0009-0003-6959-6375)
- Khobe Chandran
- Fabrizio Dal Moro
- Xiaowen Huang
- Silke Gillessen Sommer
- Pan Song
Institutions
- University of Verona (IT)
- University of Padua (IT)
- Institute of Cancer Research (GB)
- Army Medical University (CN)
- Sichuan University (CN)
- Board of the Swiss Federal Institutes of Technology (CH)
- University of Florida (US)
- ETH Zurich (CH)
- West China Hospital of Sichuan University (CN)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Ente Ospedaliero Cantonale (CH)
- Institute of Oncology Research (CH)
- Xinqiao Hospital (CN)
- Royal Marsden Hospital (GB)
- Candiolo Cancer Institute (IT)
- Università della Svizzera italiana (CH)
- Florida College (US)
Publication Details
- Journal
- Nature Cancer
- Published
- 2026-09-09
- DOI
- https://doi.org/10.1038/s43018-026-01229-9
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00