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Article History

Received: 24 October 2023

Accepted: 30 January 2024

First Online: 15 March 2024

Acknowledgements

: The authors wish to thank G. Wasney from the Structural & Biophysical Core Facility, The Hospital for Sick Children, Toronto, Canada for assistance with sEV profiling through the usage of the NanoSight NS300. In addition, we thank L. Wybenga-Groot, J. Krieger and P. Taylor of the SickKids Proteomics, Analytics, Robotics & Chemical Biology Centre, The Hospital for Sick Children, Toronto, Canada for assistance with the phospho-proteomics performed in this study. Finally, we would also like to acknowledge the services of the Research Institute of the McGill University Health Centres Clinical Proteomics Platform, McGill, Montreal, Canada for the proteomics analysis of the murine and human sEVs, along with the expertise of L. Taylor. We also gratefully acknowledge the participants who graciously contributed to the study, teams of research coordinators, as well as the clinicians and nurses who assisted with the collection of samples which were utilised in this study.

: The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Further information and requests for resources or reagents may be sent to the corresponding author.

: These studies used the resources of the Toronto General Hospital Research Institute, University Health Network, Toronto, Canada. Research on the biology of circulating EVs was supported by an Innovation Grant from the Canadian Cancer Society (no. 702835; JEF), Seed and Team Funding from the Canadian Vascular Network (MH, RSP, JEF), Project Grants from the Canadian Institutes of Health Research (PJT148487 and PJT173489; JEF), an AstraZeneca Impact Challenge Grant (RP and JEF), Canada Foundation for Innovation, John R. Evans Leaders Fund and the Ontario Research Fund. JEF received salary support through a Tier 2 Canada Research Chair in Vascular Cell and Molecular Biology from the Canadian Institutes of Health Research. PVD’s salary was supported by a Postdoctoral Fellowship from the Toronto General Hospital Research Institute. DG’s salary was supported by the Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Awards from the Canadian Institutes of Health Research, Ted Rogers Education Funding and an Ontario Graduate Scholarship. RW’s salary was supported by a Canada Graduate Scholarship from the Canadian Institutes of Health Research. None of the funders were involved in the design of the study, the collection, analysis and interpretation of data, or writing the report and did not impose any restrictions regarding the publication of the report.

: NG is the CEO of Paradox Immunotherapeutics. This study is unrelated to the work of this company. RSP discloses trial support from Vertex Pharmaceutical Inc. and consultancy fees from Sanofi but these did not influence the conduct or interpretation of this study. The other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: DG, PVD and JEF conceptualised the study. JF and RSP were responsible for participant sample selection and demographic matching. DG, PVD, XW, SG, RW, CC, KR, FA, MS, EB, NG and CL conducted the experiments. DG, PVD, RW, XW, SG and JEF were responsible for data visualisation. MH, RL, WLL, RSP, PM and JEF supervised the research and contributed to the design of the work and analysis of the data. JEF was responsible for project administration. MH, RSP and JEF were responsible for funding acquisition. DG, PVD and JEF wrote the original draft and all authors revised the manuscript. All authors approved the final version of the paper to be published. JEF accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.