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Localized Imaging of Programmed Death-Ligand 1 on Individual Tumor-Derived Extracellular Vesicles for Prediction of Immunotherapy Response
journal contributionposted on 2023-10-11, 13:37 authored by Junli Zhang, Mengting Guan, Min Lv, Yingying Liu, Hongling Zhang, Zhenzhong Zhang, Kaixiang Zhang
Programmed death-ligand 1 (PD-L1) on tumor-derived small extracellular vesicles (EVs) is a biomarker for prediction of the immunotherapy response. However, conventional bulk measurement can hardly analyze the expression of PD-L1 on individual tumor-derived EVs. Herein, a method for localized imaging of tumor-derived individual EVs PD-L1 (LITIE) is developed. In this assay, EVs in plasma were directly captured on a biochip. Then the liposome-mediated membrane fusion strategy was used to image miR-21 in EVs to discriminate miR-21-positive EVs from the whole EVs populations. Subsequently, the primer exchange reaction (PER) is applied to generate localized and amplified fluorescent signals for imaging PD-L1 on identified tumor-derived EVs. When applied in clinical sample tests, the LITIE assay could effectively distinguish breast cancer patients from healthy donors or patients with benign tumors. Interestingly, in a mice melanoma model, the LITIE assay showed the ability to predict immunotherapy response even before drug treatment. Thus, we think the strategy of measuring individual tumor-derived EVs PD-L1 could serve as an alternative way for screening clinical responders suitable for immunotherapy.
primer exchange reactionmice melanoma modelconventional bulk measurementclinical sample testsamplified fluorescent signalsderived extracellular vesicleswhole evs populationsl1 could servemeasuring individual tumorlitie assay showedderived evs pdderived evsindividual tumorpositive evsprogrammed deathlocalized imagingligand 1imaging pdimage miridentified tumorhealthy donorshardly analyzegenerate localizeddrug treatmentdiscriminate mirdirectly capturedbenign tumorsalternative way