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ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is currently difficult to treat, even when therapies are combined with immune checkpoint blockade (ICB). A novel strategy for immunotherapy would be to maximize the therapeutic potential of oncolytic viruses (OVs), which have been proven to engage the regulation of tumor microenvironment (TME) and cause-specific T-cell responses. To boost tumor sensitivity to ICB therapy, this study aimed to investigate how glutathione peroxide 4 (GPX4)-loaded OVs affect CD8+ T cells and repair the immunosuppressive environment. Here, we successfully constructed a novel recombinant oncolytic vaccinia virus (OVV) encoding the mouse GPX4 gene. We found the OVV-GPX4 effectively replicated in tumor cells and prompted the expression of GPX4 in T cells. Our research indicated that OVV-GPX4 could reshape the TME, rectify the depletion of CD8+T cells, and enhance the antitumor effects of ICB therapy.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
WW and LT analyzed data, performed experiments, drew figures and tables, and wrote the manuscript. GZ and SW funded this study, while XZ, LZ, HD, and GZ conducted experiments and statistical analysis. XT, SW, and YC designed the study, assisted with logistics, and reviewed paper drafts. Each author approved the final manuscript after this review.
Data availability statement
The results/data/figures in this manuscript have not been published elsewhere, nor are they under consideration by another publisher.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2024.2322173.