Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors
The adenosinergic pathway converting endogenous ATP to adenosine (ADO) is a major immunosuppressive pathway in cancer. Emerging data indicate that plasma small extracellular vesicles (sEV) express CD39 and CD73 and produce ADO. Using a noninvasive, highly sensitive newly developed assay, metabolism...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2444704 |
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| author | Chang Sook Hong Elizabeth V. Menchikova Yana Najjar Theresa L. Whiteside Edwin K. Jackson |
| author_facet | Chang Sook Hong Elizabeth V. Menchikova Yana Najjar Theresa L. Whiteside Edwin K. Jackson |
| author_sort | Chang Sook Hong |
| collection | DOAJ |
| description | The adenosinergic pathway converting endogenous ATP to adenosine (ADO) is a major immunosuppressive pathway in cancer. Emerging data indicate that plasma small extracellular vesicles (sEV) express CD39 and CD73 and produce ADO. Using a noninvasive, highly sensitive newly developed assay, metabolism of N6-etheno-labeled eATP, eADP or eAMP by ecto-nucleotidases on the external surface of sEV was measured using high pressure liquid chromatography with fluorescence detection. Ecto-nucleotidase activity in sEV isolated from plasma of randomly selected cancer patients and healthy donors (HDs) was compared. Relative to sEV of HDs, sEV from the plasma of melanoma patients metabolized eATP to eADP and eAMP to eADO with significantly greater efficiency. Activities of both CD39 and CD73 were elevated, as determined by the use of pharmacologic inhibitors selective for these enzymes. In contrast, metabolic activity of CD39 and CD73 on sEV isolated from plasma of patients with head and neck cancer was comparable to that of HDs, suggesting that the activity of ecto-nucleotidases on sEV may differ depending on the cancer type or cancer stage. The N6-etheno-purine assay measuring contributions of ecto-nucleotidases residing on the surface of sEV to the extracellular ATP to ADO pathway can discriminate cancer patients from HDs, differentiate among different cancer types, and potentially identify patients most likely to benefit from anti-adenosinergic therapy designed to inhibit the adenosine-mediated immune suppression. |
| format | Article |
| id | doaj-art-873476a504cb47389c546a5abacaa532 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-873476a504cb47389c546a5abacaa5322025-08-20T02:52:38ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2024.2444704Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donorsChang Sook Hong0Elizabeth V. Menchikova1Yana Najjar2Theresa L. Whiteside3Edwin K. Jackson4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USACancer Research, UPMC Hillman Cancer Center, Pittsburgh, PA, USADepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAThe adenosinergic pathway converting endogenous ATP to adenosine (ADO) is a major immunosuppressive pathway in cancer. Emerging data indicate that plasma small extracellular vesicles (sEV) express CD39 and CD73 and produce ADO. Using a noninvasive, highly sensitive newly developed assay, metabolism of N6-etheno-labeled eATP, eADP or eAMP by ecto-nucleotidases on the external surface of sEV was measured using high pressure liquid chromatography with fluorescence detection. Ecto-nucleotidase activity in sEV isolated from plasma of randomly selected cancer patients and healthy donors (HDs) was compared. Relative to sEV of HDs, sEV from the plasma of melanoma patients metabolized eATP to eADP and eAMP to eADO with significantly greater efficiency. Activities of both CD39 and CD73 were elevated, as determined by the use of pharmacologic inhibitors selective for these enzymes. In contrast, metabolic activity of CD39 and CD73 on sEV isolated from plasma of patients with head and neck cancer was comparable to that of HDs, suggesting that the activity of ecto-nucleotidases on sEV may differ depending on the cancer type or cancer stage. The N6-etheno-purine assay measuring contributions of ecto-nucleotidases residing on the surface of sEV to the extracellular ATP to ADO pathway can discriminate cancer patients from HDs, differentiate among different cancer types, and potentially identify patients most likely to benefit from anti-adenosinergic therapy designed to inhibit the adenosine-mediated immune suppression.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2444704Cancerecto-nucleotidase metabolismN6-etheno-purine assayTEXtumor-derived extracellular vesicles |
| spellingShingle | Chang Sook Hong Elizabeth V. Menchikova Yana Najjar Theresa L. Whiteside Edwin K. Jackson Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors OncoImmunology Cancer ecto-nucleotidase metabolism N6-etheno-purine assay TEX tumor-derived extracellular vesicles |
| title | Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors |
| title_full | Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors |
| title_fullStr | Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors |
| title_full_unstemmed | Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors |
| title_short | Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors |
| title_sort | assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors |
| topic | Cancer ecto-nucleotidase metabolism N6-etheno-purine assay TEX tumor-derived extracellular vesicles |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2444704 |
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