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Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy

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收录情况： ◇ 自然指数

作者：
Yang Chen[1,2] * ; Geng Haigang[1,16] * ; Yang Xupeng[3] * ; Ji Shuyi[3,4] * ; Liu Zhicheng[5] * ; Feng Hao[1] * ; Li Qian[6] ; Zhang Tangansu[7] ; Zhang Sisi[1] ; Ma Xuhui[1] ; Zhu Chuchen[1] ; Xu Nuo[1] ; Xia Yuhan[8] ; Li Yan[9] ; Wang Hongye[1] ; Yu Chune[1] ; Du Shangce[2] ; Miao Beiping[2] ; Xu Lei[5] ; Wang Hui[1] ; Cao Ying[1] ; Li Botai[10] ; Zhu Lili[1] ; Tang Xiangyu[1] ; Zhang Haoyu[1] ; Zhu Chunchao[11] ; Huang Zhao[5] ; Leng Chao[5] ; Hu Haiyan[6] ; Chen Xiaoping[5] ; Yuan Shengxian[12] ; Jin Guangzhi[13] ; Bernards Rene[14] ; Sun Chong[2] ; Zheng Quan[15] ; Qin Wenxin[1] ; Gao Qiang[3] ; Wang Cun[1] ;
机构： [1]State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute & Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Immune Regulation in Cancer Group, German Cancer Research Center (DKFZ), Heidelberg, Germany [3]Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China [4]Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China [5]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [6]Department of Oncology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [7]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, China [8]Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [9]Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [10]Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [11]Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [12]The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China [13]Department of Interventional Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [14]Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands [15]Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China [16]Present address: Department of Gastrointestinal Cancer Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
出处：
DOI： 10.1016/j.ccell.2024.10.008
ISSN：

摘要：
Tumor-initiating cells (TICs) possess the ability to evade anti-tumor immunity, potentially explaining many failures of cancer immunotherapy. Here, we identify CD49f as a prominent marker for discerning TICs in hepatocellular carcinoma (HCC), outperforming other commonly used TIC markers. CD49f-high TICs specifically recruit tumor-promoting neutrophils via the CXCL2-CXCR2 axis and create an immunosuppressive milieu in the tumor microenvironment (TME). Reciprocally, the neutrophils reprogram nearby tumor cells toward a TIC phenotype via secreting CCL4. These cells can evade CD8+ T cell-mediated killing through CCL4/STAT3-induced and CD49f-stabilized CD155 expression. Notably, while aberrant CD155 expression contributes to immune suppression, it also represents a TIC-specific vulnerability. We demonstrate that either CD155 deletion or antibody blockade significantly enhances sensitivity to anti-PD-1 therapy in preclinical HCC models. Our findings reveal a new mechanism of tumor immune evasion and provide a rationale for combining CD155 blockade with anti-PD-1/PD-L1 therapy in HCC.Copyright © 2024 Elsevier Inc. All rights reserved.

基金：
This work was funded by grants from the National Natural Science Foundation of China (82330095, 82122047, and 82473367), the Shanghai Pilot Program for Basic Research - Shanghai Jiao Tong University (21TQ1400225), the Innovative Research Team of High-Level Local Universities in Shanghai, the Central University Outstanding Youth Team Cultivation Program, the Shanghai Natural Science Foundation (22ZR1480900), the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181703), the Shanghai Cancer Institute (zz-RCPY-24-34), and the 111 Project (No. B21024).
语种：
外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 1 区 细胞生物学 1 区 肿瘤学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 细胞生物学 1 区 肿瘤学
第一作者：
第一作者机构： [1]State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute & Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Immune Regulation in Cancer Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Yang Chen,Geng Haigang,Yang Xupeng,et al.Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy[J].Cancer Cell.2024,doi:10.1016/j.ccell.2024.10.008.
APA：
Yang Chen,Geng Haigang,Yang Xupeng,Ji Shuyi,Liu Zhicheng...&Wang Cun.(2024).Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy.Cancer Cell,,
MLA：
Yang Chen,et al."Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy".Cancer Cell .(2024)

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