Plasma-derived exosomes as biomarkers for therapy monitoring in head and neck cancer patients treated with surgery and (chemo)radiotherapy

Abstract

Abstract Background Head and neck squamous cell carcinomas (HNSCC) are highly immunosuppressive and aggressive malignancies. Exosomes are small extracellular vesicles that mediate intercellular communication. HNSCC patients have a significantly higher exosome load compared to healthy donors. Here, we evaluated the potential of plasma-derived exosomes as biomarkers for therapy monitoring in advanced HNSCC treated with conventional therapy. Methods Plasma from 17 HNSCC patients was collected before, during, and after treatment by surgery with adjuvant (chemo)radiation and at time of recurrence. Total exosomal protein (TEP) of exosomes was measured to estimate exosome load. Flow cytometry was used to evaluate relative fluorescence intensity (RFI) of tumor-associated and immunoregulatory proteins on exosomes. Effects of exosomes on CD8+ T cells and adenosine production by CD39+ T cells was assessed by flow cytometry and mass spectrometry. Results TEP levels and tumor-derived exosomes varied during and after therapy with an overall decrease in the tumor-free follow up but with an increase at time of recurrence. RFI values of immune checkpoints on exosomes, their potential for T cell inhibition, and adenosine production changed during and after therapy. Recurrent patients showed a different immunoinhibitory profile compared to disease-free patients. Exosomal PD-L1 emerged as the earliest discriminator for treatment failure and disease-free survival. Conclusions Plasma-derived exosomes from HNSCC patients emerge as promising non-invasive biomarkers for early detection of treatment failure. These exosomes can accurately inform about changes in patients’ immune status and may alert of impeding recurrence.