第三军医大学朱波研究组报道，表达DNASE1L3的树突状细胞通过降解中性粒细胞胞外陷阱促进CD8⁺ T细胞功能和抗PD-(L)1治疗效果。这一研究成果于2025年8月14日发表在国际顶尖学术期刊《癌细胞》上。

该团队报道肿瘤浸润性树突状细胞（DC）特异性表达脱氧核糖核酸酶DNASE1L3与癌症患者抗PD-(L)1治疗的良好结果呈正相关。DNASE1L3在DCs中的条件敲除通过损害CD8⁺ T细胞的浸润和效应功能，导致肿瘤生长增强，降低抗PD-(L)1的治疗效果。相反，注射DNASE1L3促进CD8⁺ T细胞浸润，减少TME的衰竭，显著延缓肿瘤生长，增强抗PD-(L)1反应。DNASE1L3⁺ DCs可以降解抑制肿瘤中CD8⁺ T细胞空间分布的中性粒细胞胞外陷阱，从而在人类癌症中建立细胞毒性CD8⁺ T细胞中心。他们的发现揭示了DC在调节肿瘤内CD8⁺ T细胞中的作用，并确定了DNASE1L3是改善抗PD-(L)1治疗的有希望的靶点。

据介绍，肿瘤微环境（TME）中的CD8⁺ T细胞排斥和功能障碍是抗PD-(L)1治疗中最具挑战性的障碍之一。

附：英文原文

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

Author: Degao Chen, Zheng Jin, Han Chu, Yucui Wu, Yangping Bian, Ting Yuan, Hao Lv, Qiuyu Xia, Lei Wang, Qian Chu, Quanxing Liu, Dong Zhou, Wenfeng Fang, Xiaoming Cheng, Haoran Zha, Haixia Long, Li Zhang, Jigang Dai, Yisong Y. Wan, Qi-Jing Li, Qingzhu Jia, Xindong Liu, Bo Zhu

Issue&Volume: 2025-08-14

Abstract: 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.

DOI: 10.1016/j.ccell.2025.07.014

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00320-4