Intratumoral mycobiome heterogeneity influences the tumor microenvironment and immunotherapy outcomes in renal cell carcinoma

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-04-09 DOI:10.1126/sciadv.adu1727

Weiming Mou, Zhixing Deng, Lingxuan Zhu, Aimin Jiang, Anqi Lin, Liling Xu, Gengwen Deng, Hongsen Huang, Zeji Guo, Bang Zhu, Shuqi Wu, Tao Yang, Lu Wang, Zaoqu Liu, Ting Wei, Jian Zhang, Liang Cheng, Haojie Huang, Rui Chen, Yi Shao, Quan Cheng, Linhui Wang, Shuofeng Yuan, Peng Luo

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Abstract

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⁺ 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. Aspergillus tanneri 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.

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肿瘤内真菌组异质性影响肾细胞癌的肿瘤微环境和免疫治疗结果

肿瘤内真菌组在肿瘤微环境中起着至关重要的作用，但其对肾细胞癌（RCC）的影响尚不清楚。我们收集并定量分析了来自四个国际队列的1044名RCC患者的肿瘤内真菌组数据，其中466名患者接受了免疫治疗。根据真菌丰度将患者分为真菌群落生态缺失组和真菌群落生态繁盛组。MEF组预后较差，真菌多样性较高，脂质分解代谢下调，CD8 + T细胞耗竭。我们开发了肿瘤内真菌群特征和肿瘤内真菌群相关基因表达特征，这有力地预测了RCC和其他癌症的预后和免疫治疗结果。坦黑曲霉被认为是影响RCC预后的潜在关键真菌。我们的研究结果表明，肿瘤内真菌组抑制RCC的脂质分解代谢并诱导T细胞衰竭。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.