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Tracking interactions between TAMs and CAFs mediated by arginase-induced proline production during immune evasion of HCC
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  • Bo Tang,
  • Chuanchen Wu,
  • Yuantao Mao,
  • Xinru Qi,
  • Xin Wang,
  • Ping Li,
  • Wen Zhang
Bo Tang
Shandong Normal University School of Chemistry Chemical Engineering and Materials

Corresponding Author:tangb@sdnu.edu.cn

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Chuanchen Wu
Shandong Normal University School of Chemistry Chemical Engineering and Materials
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Yuantao Mao
Shandong Normal University School of Chemistry Chemical Engineering and Materials
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Xinru Qi
Shandong Normal University School of Chemistry Chemical Engineering and Materials
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Xin Wang
Shandong Normal University School of Chemistry Chemical Engineering and Materials
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Ping Li
Shandong Normal University School of Chemistry Chemical Engineering and Materials
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Wen Zhang
Shandong Normal University School of Chemistry Chemical Engineering and Materials
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Abstract

Synergistic changes between tumor-associated macrophages (TAMs) and tumor-associated fibroblasts (CAFs) aggravated immune evasion of hepatocellular carcinoma (HCC), however, the underlying molecular mechanisms remain elusive. Their continuous and dynamic interactions are subject to bioactive molecule changes. A real-time and in-situ monitoring method suitable for in vivo research of these processes would be indispensable but is scarce. In this study, a dual imaging strategy that tracing the TAMs and CAFs simultaneously was developed using a new arginase-specific probe and established CAFs-specific probe. The emerging roles of arginase in mediating CAFs activation in mice were explored. Results showed arginase up-regulation in TAMs, followed by proline increase. Subsequently, proline produced by TAMs initiated the activation of CAFs. Through the JAK-STAT signaling, CAFs up-regulated the PD-L1 and CTLA-4, ultimately promoting immune evasion of HCC. This study revealed a new mechanism by which TAMs and CAFs collaborate in immune evasion, providing new targets for HCC immunotherapy.
08 Feb 20241st Revision Received
08 Feb 2024Submission Checks Completed
08 Feb 2024Assigned to Editor
08 Feb 2024Reviewer(s) Assigned
10 Feb 2024Review(s) Completed, Editorial Evaluation Pending