Immunosuppressive effect of small extracellular vesicle PD-L1 is restricted by co-expression of CD80

Liu, Jin‐Yuan; Yu, Zi‐Li; Fu, Qiuyun; Zhang, Lin‐Zhou; Li, Jinbang; Wang, Min; Liu, Bing; Chen, Gang

doi:10.1038/s41416-023-02369-w

Cited by 5 publications

(6 citation statements)

References 30 publications

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“…The T sequence was assembled by two split parts in R1 S –R2 S and it has been reported that chain displacement efficiency was reduced compared with nonsplitting T sequence. , We then compared the fluorescence of H1 after incubating with R1 S –R2 S or nondividing T sequences and the chain displacement efficiency of R1 S –R2 S was calculated to be 59% (Figure S3). Next, we used EVs derived from the H1975 cell line, which has been reported to express PD-L1, to verify the formation of the R1-R2 L duplex. EVs were isolated by ultracentrifugation and verified through transmission electron microscopy (TEM), nanoparticle tracking (NTA), and Western blot (WB), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, EpCAM + and PD-L1 + EVs and CD3 + and PD-L1 + EVs were also be detected (Figure 4e,f), which proved the heterogeneity of PD-L1 + EVs sources, that is, not only tumor cells released PD-L1 + EVs into the tumor microenvironment but immune T cells also did, which is consistent with the previous literature report. 37 After the identification of subpopulations of PD-L1 + EVs, we further examined clinical plasma samples with DRMAA. EVs were isolated from the plasma of 8 healthy people and 10 NSCLC patients.…”

Section: Analysis Of Clinical Samples By Drmaa Researchers Used To Fo...mentioning

confidence: 99%

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Dual-Recognition-Mediated Autocatalytic Amplification Assay for the Subpopulations of PD-L1 Positive Extracellular Vesicle

Ren,

Ge,

Tang

et al. 2024

Anal. Chem.

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The PD-L1 protein on extracellular vesicles (EVs) is a promising biomarker for tumor immunotherapy. However, PD-L1+ EVs have various cell origins, so further analysis of the subpopulations is essential to help understand better their relationship with tumor immunotherapy. Different from the previous work which focus on the level of total PD-L1+ EVs expression, we, herein, report a dual-recognition mediated autocatalytic amplification (DRMAA) assay to detect the PD-L1 derived from tumors (EpCAM+), immune T cells (CD3+), and total (Lipids) EVs, respectively. The DRMAA assay employed proximity hybridization to construct a complete trigger sequence and then catalyzed the cross-hybridization of three hairpin probes, producing a three-way DNA junction (3-WJ) structure carrying the newly exposed trigger sequence. The 3-WJ complex subsequently initiated an autocatalytic amplification reaction and higher sensitivity than the traditional catalytic hairpin assembly assay was obtained. It was found that the EpCAM+ and PD-L1+ EVs were more effective than others in distinguishing lung cancer patients from healthy people. Surprisingly, the CD3+ and PD-L1+ EVs in lung cancer patients were also upregulated, indicating that immune cell-derived PD-L1+ EVs are also non-negligible marker in a tumor microenvironment. Our results suggested that the DRMAA assay would improve the study of subpopulations of PD-L1+ EVs to provide new insights for cancer immunotherapies.

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Section: Resultsmentioning

confidence: 99%

Section: Analysis Of Clinical Samples By Drmaa Researchers Used To Fo...mentioning

confidence: 99%

Dual-Recognition-Mediated Autocatalytic Amplification Assay for the Subpopulations of PD-L1 Positive Extracellular Vesicle

Ren,

Ge,

Tang

et al. 2024

Anal. Chem.

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“…Hundreds of such ligands have been reported, and interestingly, many of these are not exclusive to EV surfaces but also exist in a soluble form. This includes several ligands for major receptor families, such as the TNF family receptor ligands (e.g., CD95L (FasL) (Audo et al, 2012;Kim et al, 2005), TRAIL (Wajant, 2006), TNF alpha (Zhang et al, 2006), CD40L (Martínez et al, 2022), OX40L (Neyrinck-Leglantier et al, 2022, CD70 (Himbert et al, 2020), CD30L (Hansen et al, 2014(Hansen et al, , 2016 and RANKL (Wnt (Gross et al, 2012;Holliday et al, 2021))) and Wnt ligands (Torres et al, 2021) as well as ligands belonging to the Ig superfamily (e.g., PD-L1 (Martínez et al, 2022), CD80 (Liu et al, 2023), and CD66a/CEACAM1 (Igami et al, 2022)). Additionally, ligands for receptor tyrosine kinases such as VEGF (Zeng & Fu, 2019), colony-stimulating factors (Meng et al, 2021), and epidermal growth factors (Frawley & Piskareva, 2020) 2008; Li et al, 1999;Matsumoto et al, 2015;Richter et al, 2012;Suda et al, 1997).…”

Section:  the Ev Membrane As Protein Presentation Platformmentioning

confidence: 99%

Membranes on the move: The functional role of the extracellular vesicle membrane for contact‐dependent cellular signalling

Jahnke,

Staufer

2024

J of Extracellular Vesicle

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Extracellular vesicles (EVs), lipid‐enclosed structures released by virtually all life forms, have gained significant attention due to their role in intercellular and interorganismal communication. Despite their recognized importance in disease processes and therapeutic applications, fundamental questions about their primary function remain. Here, we propose a different perspective on the primary function of EVs, arguing that they serve as essential elements providing membrane area for long‐distance, contact‐dependent cellular communication based on protein‐protein interaction. While EVs have been recognized as carriers of genetic information, additional unique advantages that they could provide for cellular communication remain unclear. Here, we introduce the concept that the substantial membrane area provided by EVs allows for membrane contact‐dependent interactions that could be central to their function. This membrane area enables the lateral diffusion and sorting of membrane ligands like proteins, polysaccharides or lipids in two dimensions, promoting avidity‐driven effects and assembly of co‐stimulatory architectures at the EV‐cell interface. The concept of vesicle‐induced receptor sequestration (VIRS), for example, describes how EVs confine and focus receptors at the EV contact site, promoting a dense local concentration of receptors into signalosomes. This process can increase the signalling strength of EV‐presented ligands by 10‐1000‐fold compared to their soluble counterparts. The speculations in this perspective advance our understanding of EV‐biology and have critical implications for EV‐based applications and therapeutics. We suggest a shift in perspective from viewing EVs merely as transporters of relevant nucleic acids and proteins to considering their unique biophysical properties as presentation platforms for long‐distance, contact‐dependent signalling. We therefore highlight the functional role of the EV membrane rather than their content. We further discuss how this signalling mechanism might be exploited by virus‐transformed or cancer cells to enhance immune‐evasive mechanisms.

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“…Previous research has suggested that analyzing the genomic content of exosomes can be a promising approach for studying the mutation landscape associated with cancer, providing a potential avenue for early detection methods [ 5 , 10 , 12 , 17 , 67 , 68 ]. Exosomes not only contain mtDNA but also carry a large amount of nuclear DNA, similar to the gDNA found in cell nuclei, evenly distributed across all chromosomes; this further reveals their significance and potential influence in various biological processes [ 24 , 31 , 69 ].…”

Section: Research Progress On the Application Of Exodna In Lbmentioning

confidence: 99%

Exosomal DNA: Role in Reflecting Tumor Genetic Heterogeneity, Diagnosis, and Disease Monitoring

Xiang,

Xie,

2023

Cancers

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Extracellular vesicles (EVs), with exosomes at the forefront, are key in transferring cellular information and assorted biological materials, including nucleic acids. While exosomal RNA has been thoroughly examined, exploration into exosomal DNA (exoDNA)—which is stable and promising for cancer diagnostics—lags behind. This hybrid genetic material, combining contributions from both nuclear and mitochondrial DNA (mtDNA), is rooted in the cytoplasm. The enigmatic process concerning its cytoplasmic encapsulation continues to captivate researchers. Covering the entire genetic landscape, exoDNA encases significant oncogenic alterations in genes like TP53, ALK, and IDH1, which is vital for clinical assessment. This review delves into exosomal origins, the ins and outs of DNA encapsulation, and exoDNA’s link to tumor biology, underscoring its superiority to circulating tumor DNA in the biomarker arena for both detection and therapy. Amidst scientific progress, there are complexities in the comprehension and practical application of the exoDNA surface. Reflecting on these nuances, we chart the prospective research terrain and potential pitfalls, forging a path for future inquiry. By illuminating both the known and unknown facets of exoDNA, the objective of this review is to provide guidance to the field of liquid biopsy (LB) while minimizing the occurrence of avoidable blind spots and detours.

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Immunosuppressive effect of small extracellular vesicle PD-L1 is restricted by co-expression of CD80

Cited by 5 publications

References 30 publications

Dual-Recognition-Mediated Autocatalytic Amplification Assay for the Subpopulations of PD-L1 Positive Extracellular Vesicle

Dual-Recognition-Mediated Autocatalytic Amplification Assay for the Subpopulations of PD-L1 Positive Extracellular Vesicle

Membranes on the move: The functional role of the extracellular vesicle membrane for contact‐dependent cellular signalling

Exosomal DNA: Role in Reflecting Tumor Genetic Heterogeneity, Diagnosis, and Disease Monitoring

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