A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles

• Published in: Nature communications 2023-09, Vol.14 (1), p.5576-15, Article 5576
• Main Authors: Chen, Kangfu, Duong, Bill T. V., Ahmed, Sharif U., Dhavarasa, Piriththiv, Wang, Zongjie, Labib, Mahmoud, Flynn, Connor, Xu, Jingya, Zhang, Yi Y., Wang, Hansen, Yang, Xiaolong, Das, Jagotamoy, Zargartalebi, Hossein, Ma, Yuan, Kelley, Shana O.
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/106; 13/31; 631/1647/664/1364; 631/61/350/877; 639/925/927/1062; Biomarkers; Blood plasma; Cancer screening; CD8 antigen; Cytometry; Extracellular vesicles; Heterogeneity; Humanities and Social Sciences; Immunotherapy; Interrogation; Lymphocytes; Lymphocytes T; Medical screening; Monitoring; multidisciplinary; PD-1 protein; PD-L1 protein; Plasma; Science; Science (multidisciplinary); Subpopulations; Tumor-infiltrating lymphocytes; Tumors; Vesicles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41285-8

Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring. Exosomal PD-L1 (exoPD-L1) is a biomarker predicting immunotherapeutic responses. Here the authors report NanoEPIC, a nanoscale cytometry platform that enables phenotypic sorting and exoPD-L1 profiling from blood plasma by using magnetic-activated ranking to differentiate exosomal subpopulations.