Commensal Nakaseomyces glabratus migrates into prostate tumors to accelerate cancer progression
Menée à partir de l'analyse d'échantillons fécaux, sanguins et tumoraux issus de patients atteints d'un cancer de la prostate résistant à la castration, cette étude met en évidence un mécanisme par lequel la levure Nakaseomyces glabratus accélère la progression tumorale en migrant de l'intestin vers la tumeur et en contribuant à la résistance endocrienne via le renforcement de l'immunosuppression
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.
Nature Cancer , article en libre accès, 2026