A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles
Abstract 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 w...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41285-8 |
| _version_ | 1827709926591430656 |
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| author | Kangfu Chen Bill T. V. Duong Sharif U. Ahmed Piriththiv Dhavarasa Zongjie Wang Mahmoud Labib Connor Flynn Jingya Xu Yi Y. Zhang Hansen Wang Xiaolong Yang Jagotamoy Das Hossein Zargartalebi Yuan Ma Shana O. Kelley |
| author_facet | Kangfu Chen Bill T. V. Duong Sharif U. Ahmed Piriththiv Dhavarasa Zongjie Wang Mahmoud Labib Connor Flynn Jingya Xu Yi Y. Zhang Hansen Wang Xiaolong Yang Jagotamoy Das Hossein Zargartalebi Yuan Ma Shana O. Kelley |
| author_sort | Kangfu Chen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:30:06Z |
| format | Article |
| id | doaj.art-db1a84b8a6c24aea94bb88980dd20cfc |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:30:06Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-db1a84b8a6c24aea94bb88980dd20cfc2023-11-20T10:04:51ZengNature PortfolioNature Communications2041-17232023-09-0114111510.1038/s41467-023-41285-8A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesiclesKangfu Chen0Bill T. V. Duong1Sharif U. Ahmed2Piriththiv Dhavarasa3Zongjie Wang4Mahmoud Labib5Connor Flynn6Jingya Xu7Yi Y. Zhang8Hansen Wang9Xiaolong Yang10Jagotamoy Das11Hossein Zargartalebi12Yuan Ma13Shana O. Kelley14Department of Pharmaceutical Sciences, University of TorontoDepartment of Chemistry, University of TorontoDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Biochemistry, University of TorontoDepartment of Biomedical Engineering, Northwestern UniversityDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Chemistry, University of TorontoDepartment of Chemistry, University of TorontoDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Chemistry, Northwestern UniversityDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Pharmaceutical Sciences, University of TorontoDepartment of Pharmaceutical Sciences, University of TorontoAbstract 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.https://doi.org/10.1038/s41467-023-41285-8 |
| spellingShingle | Kangfu Chen Bill T. V. Duong Sharif U. Ahmed Piriththiv Dhavarasa Zongjie Wang Mahmoud Labib Connor Flynn Jingya Xu Yi Y. Zhang Hansen Wang Xiaolong Yang Jagotamoy Das Hossein Zargartalebi Yuan Ma Shana O. Kelley A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles Nature Communications |
| title | A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles |
| title_full | A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles |
| title_fullStr | A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles |
| title_full_unstemmed | A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles |
| title_short | A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles |
| title_sort | magneto activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles |
| url | https://doi.org/10.1038/s41467-023-41285-8 |
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