Cargo and functional profile of saliva-derived exosomes reveal biomarkers specific for head and neck cancer

BackgroundExosomes contribute to immunosuppression in head and neck squamous cell carcinoma (HNSCC), a tumor entity which lacks specific tumor biomarkers. Plasma-derived exosomes from HNSCC patients correlate with clinical parameters and have potential as liquid biopsy. Here, we investigate the carg...

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Hauptverfasser: Hofmann, Linda (VerfasserIn) , Medyany, Valentin (VerfasserIn) , Ezić, Jasmin (VerfasserIn) , Lotfi, Ramin (VerfasserIn) , Niesler, Beate (VerfasserIn) , Röth, Ralph (VerfasserIn) , Engelhardt, Daphne (VerfasserIn) , Laban, Simon Andreas (VerfasserIn) , Schuler, Patrick (VerfasserIn) , Hoffmann, Thomas K. (VerfasserIn) , Brunner, Cornelia (VerfasserIn) , Jackson, Edwin K. (VerfasserIn) , Theodoraki, Marie-Nicole (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 11 July 2022
In: Frontiers in medicine
Year: 2022, Jahrgang: 9, Pages: 1-14
ISSN:2296-858X
DOI:10.3389/fmed.2022.904295
Online-Zugang:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.3389/fmed.2022.904295
Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fmed.2022.904295
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Verfasserangaben:Linda Hofmann, Valentin Medyany, Jasmin Ezić, Ramin Lotfi, Beate Niesler, Ralph Röth, Daphne Engelhardt, Simon Laban, Patrick J. Schuler, Thomas K. Hoffmann, Cornelia Brunner, Edwin K. Jackson and Marie-Nicole Theodoraki

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245 1 0 |a Cargo and functional profile of saliva-derived exosomes reveal biomarkers specific for head and neck cancer  |c Linda Hofmann, Valentin Medyany, Jasmin Ezić, Ramin Lotfi, Beate Niesler, Ralph Röth, Daphne Engelhardt, Simon Laban, Patrick J. Schuler, Thomas K. Hoffmann, Cornelia Brunner, Edwin K. Jackson and Marie-Nicole Theodoraki 
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520 |a BackgroundExosomes contribute to immunosuppression in head and neck squamous cell carcinoma (HNSCC), a tumor entity which lacks specific tumor biomarkers. Plasma-derived exosomes from HNSCC patients correlate with clinical parameters and have potential as liquid biopsy. Here, we investigate the cargo and functional profile of saliva-derived exosomes from HNSCC patients and their potential as non-invasive biomarkers for disease detection and immunomodulation.MethodsExosomes were isolated from saliva of HNSCC patients (n = 21) and healthy donors (HD, n = 12) by differential ultracentrifugation. Surface values of immune checkpoints and tumor associated antigens on saliva-derived exosomes were analyzed by bead-based flow cytometry using CD63 capture. Upon co-incubation with saliva-derived exosomes, activity and proliferation of T cells were assessed by flow cytometry (CD69 expression, CFSE assay). Adenosine levels were measured by mass spectrometry after incubation of saliva-derived exosomes with exogenous ATP. miRNA profiling of saliva-derived exosomes was performed using the nCounter® SPRINT system.ResultsSaliva-derived, CD63-captured exosomes from HNSCC patients carried high amounts of CD44v3, PDL1 and CD39. Compared to plasma, saliva was rich in tumor-derived, CD44v3+ exosomes and poor in hematopoietic cell-derived, CD45+ exosomes. CD8+ T cell activity was attenuated by saliva-derived exosomes from HNSCC patients, while proliferation of CD4+ T cells was not affected. Further, saliva-derived exosomes produced high levels of immunosuppressive adenosine. 62 HD- and 31 HNSCC-exclusive miRNAs were identified. Samples were grouped in “Healthy” and “Cancer” based on their saliva-derived exosomal miRNA profile, which was further found to be involved in RAS/MAPK, NF-κB complex, Smad2/3, and IFN-α signaling.ConclusionsSaliva-derived exosomes from HNSCC patients were enriched in tumor-derived exosomes whose cargo and functional profile reflected an immunosuppressive TME. Surface values of CD44v3, PDL1 and CD39 on CD63-captured exosomes, adenosine production and the miRNA cargo of saliva-derived exosomes emerged as discriminators of disease and emphasized their potential as liquid biomarkers specific for HNSCC. 
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