Tracking interactions between TAMs and CAFs mediated by arginase‐induced proline production during immune evasion of HCC
Chuanchen Wu,
Yuantao Mao,
Xinru Qi,
Xin Wang,
Ping Li,
Wen Zhang,
Bo Tang
Affiliations
Chuanchen Wu
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Yuantao Mao
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Xinru Qi
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Xin Wang
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Ping Li
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Wen Zhang
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Bo Tang
College of Chemistry Chemical Engineering and Materials Science Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Key Laboratory of Molecular and Nano Probes Key Laboratory of Molecular and Nano Probes Ministry of Education Institute of Biomedical Sciences Shandong Normal University Jinan People's Republic of China
Abstract Synergistic changes between tumor‐associated macrophages (TAMs) and cancer‐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.
