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

Abstract

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.

Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma

“…Since it has been shown that EVs are involved in multisystemic signaling mediating regeneration and long-term adaptive responses [ 40 , 41 ], based on our findings as well, it is reasonable to assume that SIRT of the liver could have systemic implications on the immune system. In a recent study, a decrease in CD4 and CD8 carrying EVs was demonstrated, while the number of CD69 carrying EVs in the circulation of CCA patients was increased compared to HVs.…”

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses

“…EVs transport programmed death protein-ligand 1 (PD-L1), which interacts with PD-1 and reduces CD8 + T-cell proliferation and promotes T-cell apoptosis, which in turn reduces the immune response and leads to large-scale tumor growth. PD-L1 also blocks Ca 2+ /soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex induction and regulates exosome secretion ( 48 ). EVs carrying the CD95 ligand or tumor necrosis factor-related apoptosis-inducing ligand can induce the apoptosis of activated T cells via p53 to expose PD-L1, thereby inhibiting T-cell-mediated immunity against cancers ( 49 ).…”

Exosome-Derived Non-Coding RNAs in the Tumor Microenvironment of Colorectal Cancer: Possible Functions, Mechanisms and Clinical Applications

“…Another study showed that exosomal circPACRGL generated from CRC cells promoted neutrophil N1-N2 differentiation through the miR-142-3p/miR-506-3p-TGF-β1 axis ( 102 ). Moreover, the immune system normally responds to foreign antigens by promoting the proliferation and differentiation of cytotoxic T cells in TME ( 103 ). Xian et al.…”