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DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Chen Degao[1,2] * ; Jin Zheng[3] * ; Chu Han[1,4] * ; Wu Yucui[1,2] ; Bian Yangping[1,2] ; Yuan Ting[1,2] ; Lv Hao[1,2] ; Xia Qiuyu[5] ; Wang Lei[6] ; Chu Qian[6] ; Liu Quanxing[7] ; Zhou Dong[7] ; Fang Wenfeng[8] ; Cheng Xiaoming[9] ; Zha Haoran[10] ; Long Haixia[1,2] ; Zhang Li[8] ; Dai Jigang[7] ; Wan Yisong Y[11] ; Li Qi-Jing[12,13] ; Jia Qingzhu[1,2] ; Liu Xindong[14,15] ; Zhu Bo[1,2,3,15] ;
机构： [1]Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China [2]Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China [3]Institute of Immunological Innovation and Translation, Chongqing Medical University, Chongqing 400016, China [4]Center of Growth, Metabolism, and Aging, Key Laboratory of Bio-Resources and Eco-Environment, College of Life Sciences, Sichuan University, Chengdu 610064, China [5]School of Life Sciences, Chongqing University, Chongqing 400044, China [6]Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China [7]Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China [8]Medical Oncology Department, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [9]Department of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China [10]Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China [11]Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA [12]Institute of Molecular and Cell Biology (IMCB) and Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore [13]Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore [14]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China [15]Jinfeng Laboratory, Chongqing 401329, China
出处：
DOI： 10.1016/j.ccell.2025.07.014
ISSN：

摘要：
CD8+ T cell exclusion and dysfunction in the tumor microenvironment (TME) are among the most challenging obstacles for anti-PD-(L)1 therapy. Here, we report that tumor-infiltrating dendritic cell (DC)-specific expression of the deoxyribonuclease, DNASE1L3, is positively correlated with favorable outcomes of anti-PD-(L)1 treatment in cancer patients. DNASE1L3 conditional knockout in DCs leads to enhanced tumor growth and diminishes anti-PD-L1 therapeutic efficacy by impairing infiltration and effector functions of CD8+ T cells. Conversely, injection with DNASE1L3 promotes CD8+ T cell infiltration and reduces exhaustion in the TME, significantly retarding tumor growth and enhancing anti-PD-L1 response. DNASE1L3+ DCs can degrade neutrophil extracellular traps that suppress the spatial distribution of CD8+ T cells in tumors, enabling establishment of cytotoxic CD8+ T cell hubs in human cancers. Our findings reveal a role of DC in regulating intratumoral CD8+ T cells and identify DNASE1L3 as a promising target to improve anti-PD-(L)1 therapy.Copyright © 2025. Published by Elsevier Inc.

基金：
This work was supported by grants from National Natural Science Foundation of China (81925030 and 82230095 to B.Z.; 82073147 and 82241233 to Q.J.; 82192892, 82171742, and 92259301 to X.L.; and 82003018 to D.C.), National Key Research and Development Program of China (2023YFC2506400 to X.L.), Science and Technology Innovation Key R&D Program of Chongqing (CSTB2023TIAD-STX0007 to B.Z.; CSTB2022TIAD-STX0009 to X.L.), Natural Science Foundation of Chongqing (CSTB2022NSCQ-JQX0005 to H. Long), China Postdoctoral Science Foundation (2022TQ0137 and 2022M723869 to D.C.), R&D Program of Guangzhou Laboratory (SRPG22-006 to X.L.), and institute project grants (2022YQB059 to D.C.).
语种：
外文
被引次数：
WOS：
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中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 医学
小类 | 1 区 细胞生物学 1 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 细胞生物学 1 区 肿瘤学
JCR分区：
出版当年[2024]版：
Q1 CELL BIOLOGY Q1 ONCOLOGY
最新[2024]版：
Q1 CELL BIOLOGY Q1 ONCOLOGY

影响因子： 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

第一作者：
第一作者机构： [1]Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China [2]Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China
共同第一作者：
通讯作者：
通讯机构： [1]Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China [2]Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China [3]Institute of Immunological Innovation and Translation, Chongqing Medical University, Chongqing 400016, China [14]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China [15]Jinfeng Laboratory, Chongqing 401329, China
推荐引用方式(GB/T 7714)：
Chen Degao,Jin Zheng,Chu Han,et al.DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps[J].Cancer Cell.2025,43(9):doi:10.1016/j.ccell.2025.07.014.
APA：
Chen Degao,Jin Zheng,Chu Han,Wu Yucui,Bian Yangping...&Zhu Bo.(2025).DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps.Cancer Cell,43,(9)
MLA：
Chen Degao,et al."DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps".Cancer Cell 43..9(2025)

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