The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy

Chifei Kang; Luyu Liu; Chengyu Wu; Lingyun Li; Xiao Jia; Wendi Xie; Siyu Chen; Xinying Wu; Huaxiao Zheng; Jingxin Liu; Rongsong Li; Bin Zeng

doi:10.3389/fimmu.2023.1111369

The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy

Front Immunol. 2023 Feb 23:14:1111369. doi: 10.3389/fimmu.2023.1111369. eCollection 2023.

Authors

Chifei Kang^{1

2}, Luyu Liu³, Chengyu Wu⁴, Lingyun Li¹, Xiao Jia¹, Wendi Xie¹, Siyu Chen¹, Xinying Wu¹, Huaxiao Zheng¹, Jingxin Liu¹, Rongsong Li², Bin Zeng¹

Affiliations

¹ College of Pharmacy, Shenzhen Technology University, Shenzhen, China.
² College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen, China.
³ Guangdong Institute of Intelligence Science and Technology, Hengqin Guangdong-Macao In-Depth Cooperation Zone, Zhuhai, Guangdong, China.
⁴ Research Centre of Printed Flexible Electronics, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen, China.

Abstract

Extracellular adenosine (eADO) signaling has emerged as an increasingly important regulator of immune responses, including tumor immunity. eADO is mainly produced from extracellular ATP (eATP) hydrolysis. eATP is rapidly accumulated in the extracellular space following cell death or cellular stress triggered by hypoxia, nutrient starvation, or inflammation. eATP plays a pro-inflammatory role by binding and activating the P2 purinergic receptors (P2X and P2Y), while eADO has been reported in many studies to mediate immunosuppression by activating the P1 purinergic receptors (A1, A2A, A2B, and A3) in diverse immune cells. Consequently, the hydrolysis of eATP to eADO alters the immunosurveillance in the tumor microenvironment (TME) not only by reducing eATP levels but also by enhancing adenosine receptor signaling. The effects of both P1 and P2 purinergic receptors are not restricted to immune cells. Here we review the most up-to-date understanding of the tumor adenosinergic system in all cell types, including immune cells, tumor cells, and stromal cells in TME. The potential novel directions of future adenosinergic therapies in immuno-oncology will be discussed.

Keywords: adenosine; EADO; cancer; machinery and mechanisms; therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / metabolism
Adenosine Triphosphate / metabolism
Humans
Neoplasms*
Receptors, Purinergic P1 / metabolism
Receptors, Purinergic P2* / metabolism
Tumor Microenvironment

Substances

Adenosine
Receptors, Purinergic P2
Adenosine Triphosphate
Receptors, Purinergic P1

Grants and funding

This research received financial support by the Key Special Projects of National Key Research and Development Plan (2021YFA1301302), The Belt and Road Initiative and China-Africa Science and Technology Cooperation Project of Department of Science and Technology of Jiangxi Province (20202BDH80007), the National Natural Science Foundation of China (32200606), and the Natural Science Foundation of Top Talent of SZTU (GDRC202118), the Natural Science Foundation of Top Talent of SZTU (2020102), Shenzhen Natural Science Foundation (JCYJ20190813141001745, 20220718100823002).