Effects of Tumor-Derived Exosome Programmed Death Ligand 1 on Tumor Immunity and Clinical Applications

Abstract

Programmed death ligand 1 (PD-L1) is a typical immune surface protein that binds to programmed cell death 1 (PD-1) on T cells through its extracellular domain. Subsequently, T cell activity is inhibited, and tumor immune tolerance is enhanced. Anti-PD-1/PD-L1 immune checkpoint therapy blocks the combination of PD-1/PD-L1 and rejuvenates depleted T cells, thereby inhibiting tumor growth. Exosomes are biologically active lipid bilayer nanovesicles secreted by various cell types, which mediate signal communication between cells. Studies have shown that PD-L1 can not only be expressed on the surface of tumor cells, immune cells, and other cells in the tumor microenvironment, but also be released from tumor cells and exist in an extracellular form. In particular, exosome PD-L1 plays an unfavorable role in tumor immunosuppression. The immunomodulatory effect of exosome PD-L1 and its potential in fluid diagnosis have attracted our attention. This review aims to summarize the available evidence regarding the biological characteristics of exosome PD-L1 in tumor immunity, with a particular focus on the mechanisms in different cancers and clinical prospects. In addition, we also summarized the current possible and effective detection methods for exosome PD-L1 and proposed that exosome PD-L1 has the potential to become a target for overcoming anti-PD-1/PD-L1 antibody treatment resistance.

Protein cargo in extracellular vesicles as the key mediator in the progression of cancer

“…A study on oral squamous cell carcinoma (OSCC) revealed that macrophage polarisation toward the M2 subtype is promoted by programmed death ligand 1 (PD-L1) enriched exosomes derived from ER-stressed cancer cells. PD-L1 overexpression was linked to the poor overall survival of OSCC patients [ 205 , 206 ]. PD-L1 expression can also be enhanced in acidic TME [ 207 ].…”

The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy

“…In addition to the induction of EMT, the molecules carried by TDsEVs can activate intracellular anti-apoptotic pathways [ 33 , 34 ] and induce drug efflux or sequestration [ 35 ]. Moreover, TDsEVs can also repress antitumour immune cell responses and induce immune suppressor cells [ 36 ].

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“…Moreover, TDsEVs can also repress antitumour immune cell responses and induce immune suppressor cells [36].…”

Advances in Bioactivity of MicroRNAs of Plant-Derived Exosome-Like Nanoparticles and Milk-Derived Extracellular Vesicles

“…Extracellular vesicles (EVs) are bilayer membrane-coated vesicles released by a variety of cells. − Studies have demonstrated that the size and composition of EVs are heterogeneous and depend on the cellular source, state, and environmental conditions. ,, Accordingly, they can be classified into three types: (i) microvesicles that are formed by outward budding and fission of the plasma membrane; (ii) apoptotic bodies that are produced as blebs of cells undergoing apoptosis; and (iii) exosomes that are intraluminal vesicles (ILVs) contained in multivesicular bodies (MVBs) and released upon the fusion of MVBs with plasma membrane . Depending on the source of cells, EVs especially exosomes can be obtained using various laboratory isolation methods, such as ultracentrifugation, density gradient centrifugation, size exclusion chromatography, polymer-based precipitation, membrane filter, and immunoaffinity chromatography (Figure A), and harbor many different constituents, including a phospholipid bilayer membrane and membrane-associated proteins, as well as cytosolic components such as lipids, proteins, and RNAs (Figure B) .…”