Single-cell analyses implicate ascites in remodeling the ecosystems of primary and metastatic tumors in ovarian cancer

被引:61
作者
Zheng, Xiaocui [1 ]
Wang, Xinjing [1 ]
Cheng, Xi [2 ]
Liu, Zhaoyuan [3 ]
Yin, Yujia [1 ]
Li, Xiaoduan [1 ]
Huang, Zhihao [4 ]
Wang, Ziliang [1 ]
Guo, Wei [3 ]
Ginhoux, Florent [3 ,5 ,6 ,7 ]
Li, Ziyi [3 ]
Zhang, Zemin [8 ,9 ]
Wang, Xipeng [1 ]
机构
[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Obstet & Gynecol, Shanghai, Peoples R China
[2] Fudan Univ, Shanghai Canc Ctr, Dept Gynecol Oncol, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Sch Med, Dept Immunol & Microbiol, Shanghai, Peoples R China
[4] Analyt Biosci Ltd, Beijing, Peoples R China
[5] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore
[6] SingHealth Duke NUS Acad Med Ctr, Translat Immunol Inst, Singapore, Singapore
[7] Gustave Roussy Canc Campus, Villejuif, France
[8] Peking Univ, BIOPIC, Beijing, Peoples R China
[9] Peking Univ, Sch Life Sci, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
NK CELLS; ATLAS; MECHANISMS;
D O I
10.1038/s43018-023-00599-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Wang and colleagues perform single-cell profiling of human ovarian cancer samples from five anatomic sites, revealing dynamics of the immune microenvironment in malignant ascites and cell subtypes that may play a role in chemotherapy response. Ovarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with widespread metastases and ascites. Here, we depicted a single-cell landscape of the OC ecosystem with five tumor-relevant sites, including omentum metastasis and malignant ascites. Our data reveal the potential roles of ascites-enriched memory T cells as a pool for tumor-infiltrating exhausted CD8(+) T cells and T helper 1-like cells. Moreover, tumor-enriched macrophages exhibited a preference for monocyte-derived ontogeny, whereas macrophages in ascites were more of embryonic origin. Furthermore, we characterized MAIT and dendritic cells in malignant ascites, as well as two endothelial subsets in primary tumors as predictive biomarkers for platinum-based chemotherapy response. Taken together, our study provides a global view of the female malignant ascites ecosystem and offers valuable insights for its connection with tumor tissues and paves the way for potential markers of efficacy evaluation and therapy resistance in OC.
引用
收藏
页码:1138 / 1156
页数:39
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