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Oncolytic Vaccinia Virus Armed With CLEC2A Enhances Antitumor Immunity via ROS-Autophagy Feedback Loop and Cytokine Activation.

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Τίτλος: Oncolytic Vaccinia Virus Armed With CLEC2A Enhances Antitumor Immunity via ROS-Autophagy Feedback Loop and Cytokine Activation.
Συγγραφείς: Su J; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Zhai C; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Li Y; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Liu R; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Zhu J; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Chen K; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Zhou Y; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Ye T; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China., Li G; Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
Πηγή: Journal of medical virology [J Med Virol] 2026 Oct; Vol. 98 (10), pp. e71174.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7705876 Publication Model: Print Cited Medium: Internet ISSN: 1096-9071 (Electronic) Linking ISSN: 01466615 NLM ISO Abbreviation: J Med Virol Subsets: MEDLINE
Imprint Name(s): Publication: New York Ny : Wiley-Liss
Original Publication: New York, Liss.
Ιατρικοί όροι (MeSH): Vaccinia virus*/genetics , Vaccinia virus*/immunology , Reactive Oxygen Species*/metabolism , Cytokines*/metabolism , Lectins, C-Type*/genetics , Lectins, C-Type*/metabolism , Lectins, C-Type*/immunology , Oncolytic Viruses*/genetics , Oncolytic Viruses*/immunology , Oncolytic Virotherapy*/methods , Autophagy*, CD8-Positive T-Lymphocytes/immunology ; Melanoma/therapy ; Killer Cells, Natural/immunology ; Animals ; Humans ; Mice ; Female ; Cell Line, Tumor ; Mice, Inbred C57BL ; Disease Models, Animal
Περίληψη: Tumors often exhibit immunosuppressive microenvironments (TMEs) and present as immunologically "cold." Oncolytic viruses (OVs), particularly engineered vaccinia viruses (oncoVVs), are an encouraging therapy that directly lyses cancer cells and reprograms the TME. In this study, we evaluated the therapeutic potential of an oncolytic vaccinia virus expressing human C-type lectin domain family 2 member A (oncoVV-CLEC2A) in melanoma and ovarian cancer cells. OncoVV-CLEC2A elevated reactive oxygen species (ROS) levels, suppressed Nrf2-mediated antioxidant responses, and triggered autophagy. These changes promoted cytokine production (IL-6, IFN-α/β/γ, TNF-α) via activation of AP-1 and IRF3/7. In a B16-F10 melanoma model, oncoVV-CLEC2A increased serum levels of IFN-γ, accompanied by augmented infiltration of CD8+ T cells and activation of NK cells. Taken together, oncoVV-CLEC2A reshapes the TME by intensifying oxidative stress and autophagic activity, effectively turning "cold" tumors "hot." Notably, the mutual reinforcement between ROS production and autophagy activation not only enhances viral replication but also triggers cytokine-mediated immunity.
(© 2026 Wiley Periodicals LLC.)
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Grant Information: 42376105 Funding for this research project was provided by the National Natural Science Foundation of China; LTGY23D060001 Natural Science Foundation of Zhejiang Province
Contributed Indexing: Keywords: ROS; antitumor immunity; autophagy; cytokines; melanoma; oncoVV‐CLEC2A
Substance Nomenclature: 0 (Reactive Oxygen Species)
0 (Cytokines)
0 (Lectins, C-Type)
Entry Date(s): Date Created: 20261019 Date Completed: 20261019 Latest Revision: 20261019
Update Code: 20261019
DOI: 10.1002/jmv.71174
PMID: 42895454
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1096-9071
DOI:10.1002/jmv.71174