The unexpected PD-L1 suppression function of celery-derived extracellular vesicles improves lung cancer chemotherapy efficacy

芹菜衍生的细胞外囊泡具有意外的 PD-L1 抑制功能,可提高肺癌化疗疗效

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作者:Xin Lu, Ziwen Yu, Junjun Wang, Ao Tian, Tingyu Wu, Yirui Cheng, Qing Han, Fan Li, Weiliang Xia

Aim

The article explores celery-derived extracellular vesicles (CDEVs), characterized by high cellular uptake, low immunogenicity, and high stability, as a therapeutic strategy for antitumor nanomedicines.

Conclusion

CDEVs not only serve as drug carriers but also function as drugs themselves; as such, through a single administration of CDEVs, it is possible to combine immunotherapy and chemotherapy to achieve better effects between the two, providing a more comprehensive and effective cancer treatment strategy that promises to improve treatment outcomes and reduce the adverse effects of therapy.

Methods

The methods employed in this study include in vitro cell experiments such as co-culture, Western Blot, and flow cytometry. In vivo experiments were conducted in C57BL/6 tumor-bearing mice subcutaneously injected with Lewis lung carcinoma (LLC) cells. The experiments encompassed parameters such as survival rate, body weight, tumor size, flow cytometry, immunohistochemistry, and spectral live imaging system.

Results

Our study revealed that CDEVs could be used as drugs to effectively downregulate the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/programmed cell death ligand 1 (PD-L1) axis in lung cancer cells. In co-culture experiments, CDEVs were observed to impede the expression of PD-L1, thereby interfering with the interaction between PD-L1 and programmed death 1 (PD-1) and subsequently preventing the suppression of T cells. In in vivo distribution experiments, CDEVs loaded with paclitaxel (PTX) demonstrated better tumor targeting capabilities. Remarkably, following CDEVs-PTX treatment, CD8+ T cell levels in mice were increased, presumably leading to improved antitumor effects.

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