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Updated: Aug 15, 2026
09:15
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy
Xiaoting Liu1,2, Pengcheng Sun3, Can Chen1,2
1Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, China.
Frontiers in Immunology
|August 14, 2026
Summary
The CD73-adenosine axis creates an immunosuppressive tumor microenvironment, hindering melanoma treatment. Blocking this metabolic checkpoint offers a new strategy to overcome resistance to immune checkpoint inhibitors (ICIs).
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Immune checkpoint inhibitors (ICIs) have advanced melanoma treatment, but resistance persists.
- The CD73-adenosine axis is identified as a key metabolic immune checkpoint promoting an immunosuppressive tumor microenvironment (TME).
Purpose of the Study:
- To systematically review the CD73-adenosine axis in melanoma.
- To explore CD73 regulation, its role as a biomarker, and therapeutic strategies against it.
Main Methods:
- Literature review of the biochemical cascade of CD73-adenosine production.
- Analysis of CD73 expression regulation by hypoxia, MAPK signaling, and cytokines.
- Evaluation of CD73 as a biomarker and monitoring via liquid biopsies.
- Discussion of therapeutic interventions including antibodies, inhibitors, and gene editing.
Main Results:
- Extracellular ATP is converted to immunosuppressive adenosine by CD39 and CD73.
- CD73 expression is regulated by hypoxia-inducible factor 1-alpha (HIF-1α), MAPK signaling, TGF-β, and TNF-α.
- CD73 expression on tumor vs. immune cells has dichotomous significance; liquid biopsies show potential for monitoring.
Conclusions:
- Targeting the CD73-adenosine axis is a promising strategy to overcome resistance to ICIs in melanoma.
- Integrating adenosinergic blockade into precision immuno-oncology can improve patient outcomes.
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