Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans

• DOI: 10.1038/s41422-024-00945-0
• Publication Date: 2024-03-15T16:01:51Z
• Authors: Lin Fan; Junwei Liu; Wei Hu; Zexin Chen; Jie Lan; Tongtong Zhang; Yang Zhang; Xianpeng Wu; Zhiwei Zhong; Danyang Zhang; Jinlong Zhang; Rui Qin; Hui Chen; Yunfeng Zong; Jianmin Zhang; Bing Chen; Jun Jiang; Jifang Cheng; Jingyi Zhou; Zhiwei Gao; Zhenjie Liu; Ying Chai; Junqiang Fan; Pin Wu; Yinxuan Chen; Yuefeng Zhu; Kai Wang; Ying Yuan; Pintong Huang; Ying Zhang; Huiqin Feng; Kaichen Song; Xun Zeng; Wei Zhu; Xinyang Hu; Weiwei Yin; Wei Chen; Jian’an Wang
• Keywords: 0303 health sciences; 03 medical and health sciences; Article

Abstract Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation lipid contents and chronic inflammation. Traditional strategies primarily focus on reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue face significant risks. Another key component in progression adaptive immunity, but its potential role preventing remains unclear. To investigate this, we conducted retrospective cohort study tumor with plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces plaque size. With multi-omics single-cell analyses, comprehensively characterized plaque-specific PD-1 + T cells, which are activated pro-inflammatory. demonstrated anti-PD-1 mAb, when captured myeloid-expressed Fc gamma receptors (FcγRs), interacts expressed cells. This interaction turns mAb into substitute ligand, suppressing T-cell functions ligands-deficient context Further, prospective treated or without FcγR-binding capability. Our analysis shows capability effectively size, while does not. work suggests cell-targeting immunotherapy can be an effective strategy resolve humans.