Intratumoral mycobiome heterogeneity influences the tumor microenvironment and immunotherapy outcomes in renal cell carcinoma
The intratumoral mycobiome plays a crucial role in the tumor microenvironment, but its impact on renal cell carcinoma (RCC) remains unclear. We collected and quantitatively profiled the intratumoral mycobiome data from 1044 patients with RCC across four international cohorts, of which 466 patients received immunotherapy. Patients were stratified into mycobiota ecology-depauperate and mycobiota ecology-flourishing (MEF) groups based on fungal abundance. The MEF group had worse prognosis, higher fungal diversity, down-regulated lipid catabolism, and exhausted CD8<sup>+</sup> T cells. We developed the intratumoral mycobiota signature and intratumoral mycobiota-related genes expression signature, which robustly predicted prognosis and immunotherapy outcomes in RCC and other cancers. <i>Aspergillus tanneri</i> was identified as a potential key fungal species influencing RCC prognosis. Our findings suggest that the intratumoral mycobiome suppresses lipid catabolism and induces T cell exhaustion in RCC.
Authors
- Bo Zhu (ORCID: https://orcid.org/0000-0002-5829-9581)
- Quan Cheng (ORCID: https://orcid.org/0000-0003-2401-5349)
- Lingxuan Zhu (ORCID: https://orcid.org/0009-0001-9077-408X)
- Haojie Huang (ORCID: https://orcid.org/0000-0003-2751-6413)
- Shuofeng Yuan (ORCID: https://orcid.org/0000-0001-7996-1119)
- Peng Luo (ORCID: https://orcid.org/0000-0002-8215-2045)
- Ting Wei (ORCID: https://orcid.org/0000-0001-7840-1013)
- Weiming Mou (ORCID: https://orcid.org/0009-0007-1089-6516)
- Tao Yang (ORCID: https://orcid.org/0000-0003-1273-0089)
- Anqi Lin (ORCID: https://orcid.org/0000-0002-6324-0410)
- Aimin Jiang (ORCID: https://orcid.org/0000-0002-9563-983X)
- Liang Cheng C (ORCID: https://orcid.org/0000-0001-6049-5293)
- Rui Chen (ORCID: https://orcid.org/0000-0003-3728-2577)
- Jian Zhang (ORCID: https://orcid.org/0000-0001-7217-0111)
- Linhui Wang (ORCID: https://orcid.org/0000-0002-4056-0462)
- Gengwen Deng
- Zeji Guo
- Heqing Huang (ORCID: https://orcid.org/0000-0002-6135-9901)
- Zaoqu Liu (ORCID: https://orcid.org/0000-0002-0452-742X)
- Zhe Deng
- Liling Xu (ORCID: https://orcid.org/0009-0006-6515-3624)
- Shuqi Wu (ORCID: https://orcid.org/0000-0001-6483-4782)
- Yi Shao (ORCID: https://orcid.org/0000-0002-5842-3167)
Institutions
- Central South University (CN)
- Chinese University of Hong Kong (HK)
- Second Military Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Brown University (US)
- North Central Cancer Treatment Group (US)
- Renji Hospital (CN)
- Lianyungang Oriental Hospital (CN)
- Changhai Hospital (CN)
- Zhujiang Hospital (CN)
- Mayo Clinic in Arizona (US)
- Shanghai First People's Hospital (CN)
- University of Hong Kong - Shenzhen Hospital (CN)
- Mayo Clinic in Florida (US)
- Xiangya Hospital Central South University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Southern Medical University (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Science Advances
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1126/sciadv.adu1727
- Citations
- 24
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 25.09