CD39/CD73/A2AR pathway and cancer immunotherapy
Abstract Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases C...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-023-01733-x |
| _version_ | 1827985045416050688 |
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| author | Chenglai Xia Shuanghong Yin Kenneth K. W. To Liwu Fu |
| author_facet | Chenglai Xia Shuanghong Yin Kenneth K. W. To Liwu Fu |
| author_sort | Chenglai Xia |
| collection | DOAJ |
| description | Abstract Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 and CD73 play critical roles in reshaping an immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). The A2AR elicits its profound immunosuppressive function via regulating cAMP signaling. The increasing evidence suggests that CD39, CD73 and A2AR could be used as novel therapeutic targets for manipulating the antitumor immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway have been investigated in clinical trials as single agents or in combination with anti-PD-1/PD-L1 therapies. In this review, we provide an updated summary about the pathophysiological function of the adenosinergic pathway in cancer development, metastasis and drug resistance. The targeting of one or more components of the adenosinergic pathway for cancer therapy and circumvention of immunotherapy resistance are also discussed. Emerging biomarkers that may be used to guide the selection of CD39/CD73/A2AR-targeting treatment strategies for individual cancer patients is also deliberated. |
| first_indexed | 2024-04-09T23:07:28Z |
| format | Article |
| id | doaj.art-6d26402fc76e4c14b1abd991152338c3 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-09T23:07:28Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-6d26402fc76e4c14b1abd991152338c32023-03-22T10:35:16ZengBMCMolecular Cancer1476-45982023-03-0122111710.1186/s12943-023-01733-xCD39/CD73/A2AR pathway and cancer immunotherapyChenglai Xia0Shuanghong Yin1Kenneth K. W. To2Liwu Fu3Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical UniversityAffiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical UniversitySchool of Pharmacy, The Chinese University of Hong KongState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer CenterAbstract Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 and CD73 play critical roles in reshaping an immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). The A2AR elicits its profound immunosuppressive function via regulating cAMP signaling. The increasing evidence suggests that CD39, CD73 and A2AR could be used as novel therapeutic targets for manipulating the antitumor immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway have been investigated in clinical trials as single agents or in combination with anti-PD-1/PD-L1 therapies. In this review, we provide an updated summary about the pathophysiological function of the adenosinergic pathway in cancer development, metastasis and drug resistance. The targeting of one or more components of the adenosinergic pathway for cancer therapy and circumvention of immunotherapy resistance are also discussed. Emerging biomarkers that may be used to guide the selection of CD39/CD73/A2AR-targeting treatment strategies for individual cancer patients is also deliberated.https://doi.org/10.1186/s12943-023-01733-xImmunosuppressive tumor microenvironmentCancer immunotherapyCD39CD73Adenosine receptorA2AR |
| spellingShingle | Chenglai Xia Shuanghong Yin Kenneth K. W. To Liwu Fu CD39/CD73/A2AR pathway and cancer immunotherapy Molecular Cancer Immunosuppressive tumor microenvironment Cancer immunotherapy CD39 CD73 Adenosine receptor A2AR |
| title | CD39/CD73/A2AR pathway and cancer immunotherapy |
| title_full | CD39/CD73/A2AR pathway and cancer immunotherapy |
| title_fullStr | CD39/CD73/A2AR pathway and cancer immunotherapy |
| title_full_unstemmed | CD39/CD73/A2AR pathway and cancer immunotherapy |
| title_short | CD39/CD73/A2AR pathway and cancer immunotherapy |
| title_sort | cd39 cd73 a2ar pathway and cancer immunotherapy |
| topic | Immunosuppressive tumor microenvironment Cancer immunotherapy CD39 CD73 Adenosine receptor A2AR |
| url | https://doi.org/10.1186/s12943-023-01733-x |
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