Tracking interactions between TAMs and CAFs mediated by arginase-induced proline production during immune evasion of HCC  

作　　者：Chuanchen Wu Yuantao Mao Xinru Qi Xin Wang Ping Li Wen Zhang Bo Tang 

机构地区：[1]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 [2]Laoshan Laboratory,Qingdao,People’s Republic of China

出　　处：《Aggregate》2024年第3期439-449,共11页聚集体（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:22134004,22074083,21927811;Key Research and Development Program of Shandong Province,Grant/Award Number:2018YFJH0502;Natural Science Foundation of Shandong Province of China,Grant/Award Numbers:ZR2020ZD17,ZR2023YQ016,ZR2021QB042;Local Science and Technology Development Fund Guided by the Central Government of Shandong Province,Grant/Award Number:YDZX2022012;The Major Science and Technology Innovation Project of Shandong Province,Grant/Award Number:2021ZDSYS09。

摘　　要：Synergistic changes between tumor-associated macrophages(TAMs)and cancer-associatedfibroblasts(CAFs)aggravated immune evasion of hepatocellular carci-noma(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 strat-egy 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 sig-naling,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.

关 键 词：ARGINASE fluorescent probe immune evasion tumor-associatedfibroblasts tumor-associated macrophages 

分 类 号：R730.51[医药卫生—肿瘤]