The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies

作     者：Longsheng Wang Jie Zhang Wenxin Zhang Mingming Zheng Hongjie Guo Xiaohui Pan Wen Li Bo Yang Ling Ding 

作者机构：Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchInstitute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China The Innovation Institute for Artificial Intelligence in MedicineZhejiang UniversityHangzhou 310018China Nanhu Brain-Computer Interface InstituteHangzhou 311100China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第5期

页      面：1951-1964页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China(No.81930102 to Bo Yang,No.82273949 to Ling Ding,No.82104196 to Xi Chen) Fundamental Research Funds for the Central Universities[grant number:2021FZZX001-48] 

主　　题：Adenosine Adenosine receptors Adenosine-generating enzymes Tumor microenvironment Immune suppression Immune escape Clinical treatment Targeting drugs 

摘      要：Adenosine(Ado)is significantly elevated in the tumor microenvironment(TME)compared to normal *** binds to adenosine receptors(AdoRs),suppressing tumor antigen presentation and immune cell activation,thereby inhibiting tumor adaptive *** downregulates major histocompatibility complex II(MHC II)and co-stimulatory factors on dendritic cells(DCs)and macrophages,inhibiting antigen *** suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor(TCR)binding and signal *** also inhibits chemokine secretion and KCa3.1 channel activity,impeding effector T cell trafficking and infiltration into the tumor ***,Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion,upregulating immune checkpoint proteins,and enhancing immune-suppressive cell *** Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other *** and clinical development of inhibitors targeting Ado generation or AdoRs is ***,this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity,as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.