Quantification‐Promoted Discovery of Glycosylated Exosomal PD‐L1 as a Potential Tumor Biomarker

Abstract

Exosomal programmed cell death ligand 1 (exoPD‐L1) has emerged as a promising biomarker for cancer diagnosis and immunotherapy outcome prediction. However, the existing quantitation methods are incapable of addressing the heterogeneity of exoPD‐L1 glycosylation, which has been demonstrated to be the institutional basis for PD‐L1/PD‐1 interaction and the crucial participant in inhibiting the activity of CD8+ T cells. Herein, an aptamer‐ and lectin‐induced proximity ligation assay combined with quantitative real‐time polymerase chain reaction for precise quantitation of glycosylated exoPD‐L1 is developed. Leveraging the metabolism‐free lectin labeling of glycosylation, the glycosylation‐independent aptamer tagging of PD‐L1, and excellent selectivity of dual‐recognition, this method enables glycosylated exoPD‐L1 quantitation with high sensitivity and selectivity in a wash‐free manner. As a result, this method is able to distinguish the levels of glycosylated exoPD‐L1 between healthy donors and cancer patients with sensitivity and specificity of 100%. Compared with the total circulating exoPD‐L1 level, glycosylated exoPD‐L1 is for the first time identified to be a more reliable biomarker for tumor diagnosis. Overall, this strategy holds a great potential for revealing the significance of exoPD‐L1 glycosylation and converting glycosylated exoPD‐L1 into a reliable clinical indicator.

Combining PD-1 or PD-L1 inhibitors with chemotherapy is a good strategy for the treatment of extensive small cell lung cancer: A retrospective analysis of clinical studies

“…These clinical studies require a more detailed classification of SCLC. Fourth, it may be related to tumour immune escape mediated by exosomal PD-L1 ( 38 ). In addition to their own high expression of PD-L1 to suppress immune system-mediated immune evasion, tumour cells can also release PD-L1-carrying exosomes that are equally capable of remotely interfering with immune cell activity ( 39 , 40 ).…”

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment

“…Exosomal PD-L1 is a biomarker for tumor diagnosis and immunotherapy efficacy prediction. There is glycosylation heterogeneity in exosomal PD-L1, and the sensitivity and specificity of glycosylated exosomal PD-L1 is superior compared to exosomal PD-L1 [169]. Exosomal BECN1 participated in the regulation of ferroptosis [170].…”

Mesoporous Nanozyme-Enhanced DNA Tetrahedron Electrochemiluminescent Biosensor with Three-Dimensional Walking Nanomotor-Mediated CRISPR/Cas12a for Ultrasensitive Detection of Exosomal microRNA

“…MiRNAs are a class of short and endogenous RNA molecules, which are correlated with various diseases. − Compared with circulating miRNAs, exomiRNAs encapsulated in exosomes have merits including high content miRNAs and stability, and thus they are regarded as ideal biomarkers for early clinical diagnostics. − Although the accurate detection ability of exomiRNAs has attracted much attention with significantly diagnostic values, there remains great challenges due to their short length, high sequence homology, and low abundance. So far, conventional methods including the quantitative reverse transcription polymerase chain reaction (qRT-PCR), northern blotting, and microarrays have been employed for exomiRNA analysis. , Nevertheless, they suffer from complicated processes, high-cost instruments, or low sensitivity.…”