C1q+tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion

• DOI: 10.1136/jitc-2023-007441
• Publication Date: 2023-08-21T16:36:04Z
• Authors: Siyu Zhang; Wenbei Peng; Haolei Wang; Xuan Xiang; Linlin Ye; Xiaoshan Wei; Zihao Wang; Qianqian Xue; Long Chen; Yuan Su; Qiong Zhou
• Keywords: Immunosuppression; Reprogramming

Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to the existence abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as dominant population, impede antitumor response; however, underlying mechanisms have not been fully elucidated yet.Single-cell RNA sequencing analysis was performed portray macrophage landscape and revealed mechanism component 1q (C1q)+ TAMs. Malignant pleural effusion (MPE) human mouse used explore phenotypes functions C1q+ TAMs.C1q+ TAMs highly expressed multiple inhibitory molecules their high infiltration significantly correlated poor prognosis. promote MPE immunosuppression through impairing effects CD8+ T Mechanistically, enhance fatty acid binding protein 5 (FABP5)-mediated metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing gene expression molecules. A high-fat diet increases microenvironment, whereas low-fat ameliorates these effects. Moreover, FABP5 inhibition represses tumor progression, while enhancing efficacy ICB lung cancer.C1q+ cells promoting immunosuppression. Targeting effectively alleviates enhances therapy. great potential be therapeutic target for immunotherapy.