biostudies-literatureLiu JInnovative Research Group Project of the National Natural Science Foundation of ChinaXingliaoyingcaijihua Project of Liaoning ProvinceNatural Science Foundation of Liaoning ProvinceNational Natural Science Foundation of ChinaChina Postdoctoral Science Foundation14https://www.ebi.ac.uk/biostudies/studies/S-EPMC8796536biostudies-literatureUnknown20(1)Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8⁺ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets. Video Abstract.Cell communication and signaling : CCSExtracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies.PMC87965362020M68101681472302XLYC19020502020-BS-10382003040Peng XLi XLi HLiu JZheng HYang LHe GWei SHuang MZhang SFan QYang SfalseExtracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies.Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8⁺ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets. Video Abstract.2022-01-01T00:00:00Z2022 Jan2026-06-19T03:08:01.417Z2026-06-19T03:07:01.585ZS-EPMC87965363509049710.1186/s12964-021-00816-w