Affiliation:
1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases National Medical Center for Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China
2. Division of Hepatobiliary and Pancreatic Surgery Department of Surgery The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China
Abstract
AbstractKynurenine derivative 3‐hydroxyanthranilic acid (3‐HAA) is known to regulate the immune system and exhibit anti‐inflammatory activity by inhibiting T‐cell cytokine secretion and influencing macrophage activity. However, the definite role of 3‐HAA in the immunomodulation of hepatocellular carcinoma (HCC) is largely unexplored. An orthotopic HCC model and treated with 3‐HAA by intraperitoneal injection is developed. Furthermore, cytometry by time‐of‐flight (CyTOF) and single‐cell RNA sequencing (scRNA‐seq) analyses are carried out to define the immune landscape of HCC. It is found that 3‐HAA treatment can significantly suppress tumor growth in the HCC model and alter the level of various cytokines in plasma. CyTOF data shows that 3‐HAA significantly increases the percentage of F4/80hiCX3CR1loKi67loMHCIIhi macrophages and decreases the percentage of F4/80loCD64+PD‐L1lo macrophages. scRNA‐seq analyses demonstrate that 3‐HAA treatment is proved to regulate the function of M1 macrophages, M2 macrophages, and proliferating macrophages. Notably, 3‐HAA inhibits the proinflammatory factors TNF and IL‐6 in multiple cell subsets, including resident macrophages, proliferating macrophages, and pDCs. This study reveals the landscape of immune cell subsets in HCC in response to 3‐HAA, indicating that 3‐HAA may be a promising therapeutic target for HCC.
Funder
National Key Research and Development Program of China
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
7 articles.
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