Cao Huili, Dai Huwei, Li Songshan, Afzal Zeeshan, Wang Xinyan, Wen Zeyu, Xiao Kaiyong, Zhao Yajing, Li Jin, Yang Bin
Department of Cardiovascular, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Medical University, Taiyuan, Shanxi, China.
Sci Rep. 2025 Jul 1;15(1):20547. doi: 10.1038/s41598-025-05635-4.
Treatment with PD-1 inhibitors may cause immune-related adverse events (irAE), of which PD-1 inhibitor-associated myocarditis is a rare and highly lethal irAE. However, the mechanism of PD-1 inhibitors-induced myocarditis in individuals with tumor is still unclear. Regulatory T cells (Treg) can directly inhibit T cell proliferation and activation, and also produce inhibitory cytokines with potent immunosuppressive properties. Deletion or aberrant function of Treg usually leads to autoimmune diseases. But reports on the role of Treg in PD-1 inhibitor-associated myocarditis are still very limited, and its role in the pathogenesis of myocarditis needs to be further explored. In addition, alterations in the composition of the gut microbiota and its metabolites have been shown to be involved in the development of several cardiovascular and autoimmune diseases. Therefore, we designed this experiment initially to investigate the role of gut microbiota in PD-1 inhibitor-associated myocarditis. Our studies showed that PD-1 inhibitors induced myocarditis and significant reduction of intracardiac Tregs in melanoma mice. It is highly likely that alterations in the composition of the gut microbiota due to PD-1 inhibitors played a key role in this process.
使用PD-1抑制剂进行治疗可能会引发免疫相关不良事件（irAE），其中PD-1抑制剂相关心肌炎是一种罕见且具有高度致死性的irAE。然而，肿瘤患者中PD-1抑制剂诱发心肌炎的机制仍不清楚。调节性T细胞（Treg）可直接抑制T细胞增殖和活化，还能产生具有强大免疫抑制特性的抑制性细胞因子。Treg的缺失或功能异常通常会导致自身免疫性疾病。但关于Treg在PD-1抑制剂相关心肌炎中作用的报道仍然非常有限，其在心肌炎发病机制中的作用有待进一步探索。此外，肠道微生物群及其代谢产物组成的改变已被证明与多种心血管疾病和自身免疫性疾病的发生有关。因此，我们最初设计了本实验来研究肠道微生物群在PD-1抑制剂相关心肌炎中的作用。我们的研究表明，PD-1抑制剂可诱发黑色素瘤小鼠发生心肌炎，并导致心脏内Treg显著减少。很可能是PD-1抑制剂导致的肠道微生物群组成改变在此过程中起了关键作用。
