Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy  

作　　者：Lei Yang Yi Zhang Li Yang 

机构地区：[1]Biotherapy Center and Cancer Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China [2]School of Life Sciences,Zhengzhou University,Zhengzhou 450052,China [3]Key Laboratory for Tumor Immunology and Biotherapy of Henan Province,Zhengzhou 450052,China

出　　处：《Cancer Biology & Medicine》2024年第11期995-1011,共17页癌症生物学与医学(英文版)

基　　金：supported by grants from the State’s Key Project of Research and Development Plan(Grant No.2021YFE0110600);the National Natural Science Foundation of China(Grant Nos.82072578 and 82350121);the Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University(Grant No.ZYCXTD2023013)。

摘　　要：This review examined the critical role of adenosine signaling in modulating the behavior of tumor-associated macrophages(TAMs),a key determinant of the tumor microenvironment(TME).Adenosine is an immunosuppressive metabolite that is highly enriched in the TME due to elevated expression of adenosine triphosphatase(ATPase).Adenosine influences polarization of TAMs through A2A and A2B receptors,which drives a phenotype that supports tumor progression and immune evasion.The adenosine-mediated regulation of TAMs significantly suppresses the TME,dampening the efficacy of current immunotherapies.Targeting the adenosine pathway has shown potential in preclinical studies through reversal of the immunosuppressive microenvironment and antitumor immune response enhancement.Clinical trials are currently underway to determine the impact of A2A receptor antagonists,and CD39 and CD73 inhibition,enzymes that are pivotal in adenosine production,in various cancers.The current understanding of the CD39-CD73-adenosine axis in TAM regulation and the emerging strategies targeting adenosine signaling pathway for therapeutic intervention are the subjects of this review.The current clinical trials focusing on adenosine pathway inhibitors in combination with existing therapies to improve clinical outcomes are summarized and the need for continued research to refine these approaches for cancer treatment is emphasized.

关 键 词：Adenosine signaling CD39 CD73 tumor associated macrophages cancer therapy 

分 类 号：R73[医药卫生—肿瘤]