Effects of 3‐HAA on HCC by Regulating the Heterogeneous Macrophages—A scRNA‐Seq Analysis

• DOI: 10.1002/advs.202207074
• Publication Date: 2023-04-04T07:28:34Z
• Authors: Chen Xue; Xinyu Gu; Qiuxian Zheng; Qingmiao Shi; Xin Yuan; Qingfei Chu; Junjun Jia; Yuanshuai Su; Zhengyi Bao; Juan Lu; Lanjuan Li
• Keywords: Carcinoma, Hepatocellular; Science; Macrophages; Q; Liver Neoplasms; hepatocellular carcinoma; macrophage; Single-Cell Gene Expression Analysis; 3. Good health; single‐cell RNA sequencing; Humans; Cytokines; 3‐hydroxyanthronic acid; cytometry by time‐of‐flight; Research Articles

Abstract Kynurenine derivative 3‐hydroxyanthranilic acid (3‐HAA) is known to regulate the immune system and exhibit anti‐inflammatory activity by inhibiting T‐cell cytokine secretion influencing macrophage activity. However, definite role of 3‐HAA in immunomodulation hepatocellular carcinoma (HCC) largely unexplored. An orthotopic HCC model treated with intraperitoneal injection developed. Furthermore, cytometry time‐of‐flight (CyTOF) single‐cell RNA sequencing (scRNA‐seq) analyses are carried out define landscape HCC. It found that treatment can significantly suppress tumor growth alter level various cytokines plasma. CyTOF data shows increases percentage F4/80 hi CX3CR1 lo Ki67 MHCII macrophages decreases CD64 + PD‐L1 macrophages. scRNA‐seq demonstrate proved function M1 macrophages, M2 proliferating Notably, inhibits proinflammatory factors TNF IL‐6 multiple cell subsets, including resident pDCs. This study reveals subsets response 3‐HAA, indicating may be a promising therapeutic target for