Abstract
The exosome serves as a trafficking vehicle for transport of programmed death-ligand 1 (PD-L1) into receptor cells. In tumor microenvironment, distant tumor cells can remotely attack activated T cells by exosomal PD-L1. Here, we summerize the biogenesis and transport process of exosomal PD-L1. Then, we focus on the cancer biology of exosomal PD-L1 in immunosuppression and the mechanism by which it inhibits T cells. Finally, we highlight the prospects of exosomal PD-L1 as a tumor biomarker and its significance in immunotherapy. In addition, we discuss the new challenges faced in researching and utilizing exosomal PD-L1. This review may shed light on the exosomal PD-L1 from the bench to the clinic. Exosomes serve as trafficking vehicles for transport of programmed death-ligand 1 (PD-L1) into receptor cells. In tumor microenvironment, distant tumor cells can remotely attack activated T cells through exosomal PD-L1. Here, we have summarized the biogenesis and transport of exosomal PD-L1. Next, we focused on the cancer biology of exosomal PD-L1 in immunosuppression and the mechanism by which it inhibits T cells. Finally, we highlighted the prospects of exosomal PD-L1 as a tumor biomarker and its significance in immunotherapy. In addition, we have discussed the new challenges faced in studying and utilizing exosomal PD-L1. This review may shed light on the translation of exosomal PD-L1 from bench to clinic.
Highlights
Programmed death-ligand 1 (PD-L1, known as CD274) is a membrane-bound ligand found on the cell surface of many tumor cell types that are upregulated in oncogenic lesions [1]
Endosomal sorting complexes required for transport (ESCRT), endosomal sorting complexes required for transport; HRS, hepatocyte growth factor receptor substrate; TSG101, tumor susceptibility gene 101 protein; STAM, signal transducing adaptor molecule; MVB, multivesicular bodies; PM, plasma membrane; VPS, Vacuolar protein sorting homolog; ALIX, ALG2-interacting protein X; Rabs, RAS related proteins; trans-Golgi network (TGN), trans Golgi network; sensitive fusion factor attachment protein receptors (SNAREs), soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor; nSMase2, neutral sphingomyelinase 2; SMPD3, Sphingomyelin Phosphodiesterase 3
We have systematically summarized and discussed the latest studies on exosomal programmed death-ligand 1 (PD-L1), including the biogenesis and transport of exosomal PD-L1, its role in immunosuppression, and the mechanism by which it inhibits T cells
Summary
Programmed death-ligand 1 (PD-L1, known as CD274) is a membrane-bound ligand found on the cell surface of many tumor cell types that are upregulated in oncogenic lesions [1]. These studies suggested that targeting any step of the biogenesis or a regulatory molecule of exosomes might affect the level of exosomal PDL1, and may result in a new method for inhibition of tumor metastasis and a novel strategy for addressing the resistance of tumors to immunotherapy. Poggio et al reported that exosomal PD-L1 systematically acts to suppress the anti-tumor immune response in prostate cancer, and its genetic blockage promotes T cell activity in draining lymph nodes to induce
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