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• W4361812649 abstract "<div>AbstractPurpose:<p>Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[¹⁸F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[¹⁸F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.</p>Experimental Design:<p>We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[¹⁸F]FDG and anti–PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis.</p>Results:<p>PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[¹⁸F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[¹⁸F]FDG stimulation and ICB was used. In addition, combination of 2-[¹⁸F]FDG with αPD-L1 mAb could reprogram a TME from “cold” to “hot,” to make low immunoactivity tumors sensitive to ICB therapy.</p>Conclusions:<p>In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[¹⁸F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[¹⁸F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.</p></div>" @default.
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• W4361812649 date "2023-03-31" @default.
• W4361812649 modified "2023-09-24" @default.
• W4361812649 title "Data from A Paradigm of Cancer Immunotherapy Based on 2-[¹⁸F]FDG and Anti–PD-L1 mAb Combination to Enhance the Antitumor Effect" @default.
• W4361812649 doi "https://doi.org/10.1158/1078-0432.c.6532302.v1" @default.
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