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

Xue, Chen; Gu, Xinyu; Zheng, Qiuxian; Shi, Qingmiao; Chu, Qingfei; Jia, Junjun; Su, Yuanshuai; Bao, Zhengyi; Lu, Juan; Li, Lanjuan

doi:10.1002/advs.202207074

Cited by 5 publications

(1 citation statement)

References 40 publications

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“…The kynurenine derivative 3-hydroxyanthranilic acid has been shown to signi cantly suppress tumor growth in the HCC model by decreasing the percentage of F4/80lo CD64 PD-L1 + lo macrophages [50]. Furthermore, Tang et al identi ed a potential increase in HCC risk associated with CD14 on CD14 + CD16-monocytes, aligning with our ndings that CD64 on CD14-CD16 + monocyte is associated with an increased risk of HCC.…”

Section: Discussionsupporting

confidence: 90%

Causal effect between immunocytes, plasma metabolites, and hepatocellular carcinoma: a bidirectional two-sample Mendelian randomization study and mediation analysis

Tang,

Xue,

Zhang

et al. 2024

Preprint

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Background Hepatocellular carcinoma (HCC) is a primary malignant liver tumor, characterized by a notably low 5-year survival rate and a high mortality rate globally. This study aimed to investigate the causal effect between immune cell phenotypes, plasma metabolites, and HCC. Methods Summary statistics of 731 immunocytes traits (N = 3,757), 1,400 plasma metabolite traits (N = 8,299) and HCC trait (N = 197,611) were obtained from publicly available genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was applied to infer the causal links using inverse variance-weighted, simple mode, MR-Egger, weighted median, and weighted mode. Several sensitivity analyses were performed to ensure reliable MR results. Finally, we used mediation analysis to identify the pathway from immunocytes to mediated by plasma metabolites. Results Causal relationships were identified among the 20 immune cell phenotypes and HCC with one exhibiting reverse causality. Additionally, 36 metabolites were causally related to HCC. Based on known causal metabolites, we observed that the glycerophospholipid metabolism pathway is closely related to HCC. Utilizing two-step MR analysis, 11 cell phenotypes were determined to have causal relationships with HCC mediated by 14 plasma metabolites, with Linolenate [alpha or gamma; (18:3n3 or 6)] levels showing the highest mediation proportion (19.3%). Conclusion Our findings affirm a causal relationship between immune cell phenotypes, plasma metabolites, and HCC, computing the proportion of the effect mediated by plasma metabolites. This study provides novel insights into the prevention, diagnosis, and treatment of HCC.

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Section: Discussionsupporting

confidence: 90%

Causal effect between immunocytes, plasma metabolites, and hepatocellular carcinoma: a bidirectional two-sample Mendelian randomization study and mediation analysis

Tang,

Xue,

Zhang

et al. 2024

Preprint

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

Xue

Zheng

et al. 2023

Advanced Science

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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 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 F4/80 hi CX3CR1 lo Ki67 lo MHCII hi macrophages and decreases the percentage of F4/80 lo CD64 + PD-L1 lo 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.

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Tryptophan metabolism in health and disease

et al. 2023

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

Cited by 5 publications

References 40 publications

Causal effect between immunocytes, plasma metabolites, and hepatocellular carcinoma: a bidirectional two-sample Mendelian randomization study and mediation analysis

Causal effect between immunocytes, plasma metabolites, and hepatocellular carcinoma: a bidirectional two-sample Mendelian randomization study and mediation analysis

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

Tryptophan metabolism in health and disease

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