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Progress for targeting adenosine A2A receptors in cancer immunotherapy
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Zhi-jing ZHANG1, Qi-yi ZHANG1, Zu-yi JIN1, Kai ZHU2, Wen DING1, *, Xiao-lei ZHANG1, *
Acta Pharmaceutica Sinica | 2022, 57(9) : 2557 - 2569
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Acta Pharmaceutica Sinica | 2022, 57(9): 2557-2569
Special Reports: Therapeutic interventions and strategies for cancer immunotherapy
Progress for targeting adenosine A2A receptors in cancer immunotherapy
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Zhi-jing ZHANG1, Qi-yi ZHANG1, Zu-yi JIN1, Kai ZHU2, Wen DING1, *, Xiao-lei ZHANG1, *
Affiliations
  • 1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
  • 2. Changchun University of Chinese Medicine, Changchun 130117, China
Published: 2022-09-12 doi: 10.16438/j.0513-4870.2022-0199
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Immunotherapy has completely changed the paradigm of clinical tumor treatment, but immune checkpoint inhibitors still have low objective response rates and are prone to drug resistance for most solid tumors. The immune suppression tumor microenvironment and complicated tumor immune escape mechanisms are key factors that affect the clinical outcome and response rates. Therefore, it is critical to reverse the obstacle of the tumor microenvironment to improve immunotherapy efficacy. The immune suppression caused by the increased level of adenosine in the tumor microenvironment raises the attention of people. Targeting adenosine receptors, especially A2AR, will be an effective strategy to improve immunotherapy efficacy. Targeting the adenosine-A2A pathway can increase immune infiltration, enhance immune cell function, and partially reverse immunotherapy-insensitive "cold tumors" to "hot tumors" to enhance treatment response rates and improve the efficacy of current immunotherapy. At present, many adenosine receptor inhibitors have shown good results in clinical trials, especially in combination with immune checkpoint inhibitors, chemotherapy, and adoptive cell transfer therapeutic drugs, which are expected to be used for tumor immunotherapy to bring new breakthroughs. This article reviews the accumulation mode of adenosine in the tumor microenvironment, the role of A2AR and their regulatory mechanism in immune response, the progress of A2AR inhibitors in clinical trials, potential risks to target A2AR, and the prospects for therapeutic targeting A2AR.

immunotherapy  /  tumor microenvironment  /  adenosine receptor  /  A2AR inhibitor  /  cancer immunotherapy drug
Zhi-jing ZHANG, Qi-yi ZHANG, Zu-yi JIN, Kai ZHU, Wen DING, Xiao-lei ZHANG. Progress for targeting adenosine A2A receptors in cancer immunotherapy[J]. Acta Pharmaceutica Sinica, 2022 , 57 (9) : 2557 -2569 . DOI: 10.16438/j.0513-4870.2022-0199
Year 2022 volume 57 Issue 9
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doi: 10.16438/j.0513-4870.2022-0199
  • Receive Date:2022-02-16
  • Online Date:2025-12-24
  • Published:2022-09-12
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  • Received:2022-02-16
  • Revised:2022-03-17
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    1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
    2. Changchun University of Chinese Medicine, Changchun 130117, China
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Family
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Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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