ArticleJournal for immunotherapy of cancer2026
CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
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9 authors.
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Abstract
backgroundOncolytic herpes simplex virus (oHSV) therapy is a live virus-based immunotherapy that lyses tumor cells which release antigens and activate antitumor immunity. oHSV therapy has been shown to increase ATP production and release of extracellular ATP (eATP). In the extracellular tumor microenvironment, eATP functions as an immune-activating damage-associated molecular pattern but is hydrolyzed to extracellular adenosine (eADO), which can be immune-suppressive. eADO is generated by the sequential action of ectoenzymes CD39 and CD73 (
methodsWe evaluated changes in eADO signaling in vitro and in patient specimens after virotherapy. A genetic CD73 knock-out mouse model and blocking antibodies were used to assess the impact of CD73 on virotherapy in two different solid tumor models. Single-cell RNA sequencing was employed to assess changes in immune cell infiltration and communication. Flow cytometric immunophenotyping and immunofluorescent imaging were utilized to confirm single-cell sequencing predicted changes in tumor microenvironment.
resultsTranscriptomic analysis of patient tumors pre-virotherapy and post-virotherapy with CAN-3110 revealed increased expression of the adenosine receptor gene
conclusionsHere, we identify that immunosuppressive eADO signaling in the TME is a major barrier to oHSV therapy and CD73 blockade prevents tumor immune escape. The combination of oHSV with CD73 blockade supports the development of an antitumor immune memory response in solid tumors. This study supports clinical development of this combination strategy.
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