上海交通大学医学院王慧、同济大学张鹏以及中科院巴斯德所陈昌斌课题组合作表明肿瘤内真菌组通过髓源性抑制细胞促进肺癌进展。相关论文发表在2023年9月21日出版的《癌细胞》杂志上。

利用真菌富集的DNA提取和深度散弹枪宏基因组测序，他们在肺腺癌(LUAD)患者中鉴定了富集的肿瘤驻留曲霉。通过三种不同的同基因肺癌小鼠模型，他们发现雪梨通过IL-1β介导的MDSCs的扩增和激活促进肺肿瘤的进展，从而抑制细胞毒性T淋巴细胞的活性和PD-1+ CD8+ T细胞的积累。这是通过β-葡聚糖/Dectin-1/CARD9途径分泌IL-1β介导的。对人类样本的分析证实，富含A. sydowii与免疫抑制和患者预后差有关。

他们的研究结果表明，尽管肿瘤内真菌组的生物量很低，但它促进了肺癌的进展，并且可以在菌株水平上靶向改善LUAD患者的预后。

据悉，尽管多态微生物组已经成为癌症的标志，但人们对肿瘤内真菌组作为活微生物在癌症进展中的作用知之甚少。

附：英文原文

Title: The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells

Author: Ning-Ning Liu, Cheng-Xiang Yi, Lu-Qi Wei, Jin-An Zhou, Tong Jiang, Cong-Cong Hu, Lu Wang, Yuan-Yuan Wang, Yun Zou, Yi-Kai Zhao, Le-Le Zhang, Ya-Ting Nie, Yi-Jing Zhu, Xin-Yao Yi, Ling-Bing Zeng, Jing-Quan Li, Xiao-Tian Huang, Hong-Bin Ji, Zisis Kozlakidis, Lin Zhong, Christopher Heeschen, Xiao-Qi Zheng, Changbin Chen, Peng Zhang, Hui Wang

Issue&Volume: 2023-09-21

Abstract: Although polymorphic microbiomes have emerged as hallmarks of cancer, far less isknown about the role of the intratumor mycobiome as living microorganisms in cancerprogression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomicsequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancermice models, we find that A. sydowii promotes lung tumor progression via IL-1β-mediated expansion and activation of MDSCs,resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulationof PD-1+ CD8+ T cells. This is mediated by IL-1β secretion via β-glucan/Dectin-1/CARD9 pathway.Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggestthat intratumor mycobiome, albeit at low biomass, promotes lung cancer progressionand could be targeted at the strain level to improve patients with LUAD outcome.

DOI: 10.1016/j.ccell.2023.08.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00288-X