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

Author

Listed:
  • Kangfu Chen

    (University of Toronto)

  • Bill T. V. Duong

    (University of Toronto)

  • Sharif U. Ahmed

    (University of Toronto)

  • Piriththiv Dhavarasa

    (University of Toronto)

  • Zongjie Wang

    (Northwestern University)

  • Mahmoud Labib

    (University of Toronto
    Northwestern University
    University of Plymouth)

  • Connor Flynn

    (University of Toronto
    Northwestern University)

  • Jingya Xu

    (University of Toronto)

  • Yi Y. Zhang

    (University of Toronto)

  • Hansen Wang

    (University of Toronto)

  • Xiaolong Yang

    (University of Toronto)

  • Jagotamoy Das

    (Northwestern University)

  • Hossein Zargartalebi

    (University of Toronto)

  • Yuan Ma

    (University of Toronto)

  • Shana O. Kelley

    (University of Toronto
    University of Toronto
    University of Toronto
    Northwestern University)

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.

Suggested Citation

  • 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 , 2023. "A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41285-8
    DOI: 10.1038/s41467-023-41285-8
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    References listed on IDEAS

    as
    1. Huilin Shao & Jaehoon Chung & Kyungheon Lee & Leonora Balaj & Changwook Min & Bob S. Carter & Fred H. Hochberg & Xandra O. Breakefield & Hakho Lee & Ralph Weissleder, 2015. "Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    2. Gang Chen & Alexander C. Huang & Wei Zhang & Gao Zhang & Min Wu & Wei Xu & Zili Yu & Jiegang Yang & Beike Wang & Honghong Sun & Houfu Xia & Qiwen Man & Wenqun Zhong & Leonardo F. Antelo & Bin Wu & Xue, 2018. "Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response," Nature, Nature, vol. 560(7718), pages 382-386, August.
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