线粒体转录因子A（TFAM）是一种转录因子，它维持着线粒体DNA（mtDNA）的稳定并启动mtDNA复制。然而，在肿瘤免疫调节功能和免疫细胞中TFAM表达方面，我们知之甚少。我们应用小鼠肿瘤模型，分析了巨噬细胞系的TFAM缺陷对肿瘤进展和肿瘤微环境（TME）改变的影响。在体外，利用原代小鼠骨髓源性树突状细胞（BMDCs）研究了变异功能和激活通路。在体内用OVA作为模型抗原来验证免疫反应的激活。利用STING抑制剂来确认由于DCs中Tfam缺失而引起的STING激活。 DCs中TFAM的删减导致线粒体功能障碍和mtDNA胞浆泄漏，从而激活了DCs中的cGAS-STING通路，促进了抗原呈递的增强。DCs中TFAM的删除有趣地逆转了免疫抑制的TME，抑制了肿瘤生长和转移。我们揭示了TFAM在DCs中的缺失通过STING途径改善了免疫抑制的肿瘤微环境。我们的研究表明，特异性DCs中TFAM敲除可能是未来设计新型免疫疗法的有效策略。©作者（或其雇主）2023。在CC BY-NC下允许重複使用。不允许商业再利用。由BMJ出版。

Mitochondrial transcription factor A (TFAM) is a transcription factor that maintains mitochondrial DNA (mtDNA) stabilization and initiates mtDNA replication. However, little is known about the immune regulation function and TFAM expression in immune cells in the tumors.Mouse tumor models were applied to analyze the effect of TFAM deficiency in myeloid cell lineage on tumor progression and tumor microenvironment (TME) modification. In vitro, primary mouse bone marrow-derived dendritic cells (BMDCs) were used in the investigation of the altered function and the activated pathway. OVA was used as the model antigen to validate the activation of immune responses in vivo. STING inhibitors were used to confirm the STING activation provoked by Tfam deficient in DCs.The deletion of TFAM in DCs led to mitochondrial dysfunction and mtDNA cytosolic leakage resulting in the cGAS-STING pathway activation in DCs, which contributed to the enhanced antigen presentation. The deletion of TFAM in DCs has interestingly reversed the immune suppressive TME and inhibited tumor growth and metastasis in tumor models.We have revealed that TFAM knockout in DCs ameliorated immune-suppressive microenvironment in tumors through STING pathway. Our work suggests that specific TFAM knockout in DCs might be a compelling strategy for designing novel immunotherapy methods in the future.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.