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
Aggregate ›› 2024, Vol. 5 ›› Issue (3) : 530
Tracking interactions between TAMs and CAFs mediated by arginase-induced proline production during immune evasion of HCC
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.
arginase / fluorescent probe / immune evasion / tumor-associated fibroblasts / tumor-associated macrophages
2024 The Authors. Aggregate published by SCUT, AIEI and John Wiley & Sons Australia, Ltd.
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