4.7 Review

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

Journal

CELL COMMUNICATION AND SIGNALING
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12964-021-00816-w

Keywords

PD-L1; Extracellular vesicles; Immune escape; Biomarker; Immunotherapy

Categories

Funding

  1. National Natural Science Foundation of China [81472302, 82003040]
  2. Natural Science Foundation of Liaoning Province [2020-BS-103]
  3. China Postdoctoral Science Foundation [2020M681016]
  4. Xingliaoyingcaijihua Project of Liaoning Province [XLYC1902050]
  5. Qingnianyingcaijihua Project of China Medical University

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PD-L1 is a ligand for PD-1 and is associated with immunosuppression. PD-L1 is not only found on the surface of tumor cells, but also on the surface of extracellular vesicles secreted by these cells. Interaction between extracellular vesicle PD-L1 and PD-1 on T cells leads to immunosuppression. Exploring the production, regulation, tumor immunosuppression, and clinical application of extracellular vesicle PD-L1 is of great importance.
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.

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