在这项研究中，该研究组证实了肿瘤内的cDC1s表现出离散的线粒体状态，并且OPA1介导的线粒体能量和氧化还原代谢决定了cDC1的抗肿瘤反应。在机制上，OPA1通过促进核呼吸因子1（NRF1）的表达和电子传递链的完整性来协调抗原呈递和cDC1s的CD8+ T细胞启动功能，从而支持生物能量学和NAD+/NADH平衡。在肿瘤进展过程中，肿瘤内cDC1s的线粒体膜电位和体积以及OPA1-NRF1信号传导均下降。
此外，肿瘤内给药具有极化线粒体的cDC1s在小鼠中显示出免疫治疗益处，特别是与免疫检查点阻断联合使用。总的来说，他们的发现揭示了线粒体代谢和信号作为癌症免疫治疗中激活cDC1功能的假定靶点。
据悉，抗肿瘤免疫需要常规的1型树突状细胞（cDC1s）。cDC1s如何在肿瘤微环境中维持功能适应度尚不清楚。
附：英文原文
Title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity
Author: Zhiyuan You, Jiyeon Kim, Chuansheng Guo, Haoran Hu, Nicole M. Chapman, Xiaoxi Meng, Hao Shi, Yan Wang, Cliff Guy, Anil KC, Jia Li, Jordy Saravia, Gustavo Palacios, Sherri Rankin, Camenzind G. Robinson, Hongbo Chi
Issue&Volume: 2026-04-02
Abstract: Antitumor immunity requires conventional type 1 dendritic cells (cDC1s). How cDC1s maintain functional fitness in the tumor microenvironment remains unclear. In this study, we established that intratumoral cDC1s exhibited discrete mitochondrial states and that OPA1-mediated mitochondrial energy and redox metabolism dictated cDC1 antitumor responses. Mechanistically, OPA1 orchestrated antigen presentation and the CD8+ T cell priming function of cDC1s by promoting nuclear respiratory factor 1 (NRF1) expression and electron transport chain integrity, thereby supporting bioenergetics and NAD+/NADH balance. During tumor progression, mitochondrial membrane potential and volume, as well as OPA1-NRF1 signaling, declined in intratumoral cDC1s. Furthermore, intratumoral administration of cDC1s with polarized mitochondria showed immunotherapeutic benefits in mice, particularly in combination with immune checkpoint blockade. Collectively, our findings reveal mitochondrial metabolism and signaling as putative targets to reinvigorate cDC1 function for cancer immunotherapy.
DOI: adv6582
Source: https://www.science.org/doi/10.1126/science.adv6582