Characterization of circulating exosomes as biomarkers for therapy monitoring in Head and Neck cancer (HNSCC) patients

Background Head and neck squamous cell carcinomas (HNSCC) are characterized by profound immunosuppression. HNSCC patients have a significantly higher exosome load compared to healthy donors. These exosomes have not only been shown to carry immunosuppressive molecules but they also correlate with clinical parameters. Here, we analyze their potential as biomarkers for short and long-term therapy monitoring.

Methods In a prospective observation-study (IRECT), plasma samples from 20 HNSCC patients were collected before, during and after different therapies as well as at time point of recurrence. Additionally, 6 healthy donors were included. Exosomes were isolated by mini size exclusion chromatography. The protein concentration was measured to estimate exosome load. Further, surface levels of immune checkpoint molecules were analyzed by on-bead flow cytometry.

Results The protein concentration of the exosome fraction increased shortly after surgery but with significant decrease during and after R(C)T. The lowest exosome load was visible 12 months after therapy. At time point of recurrence, increased exosome levels were measured. PDL-1 levels on exosomes decreased after surgery but with a significant increase 3 months after R(C)T. Both OX-40 and OX40-L levels were decreased after surgery. OX-40 levels increased 3 months after R(C)T whereas OX40-L levels remained decreased.

Conclusion The exosome load varied during and after therapy with an overall decrease in the tumor-free follow up period but with an increase at time point of recurrence. Furthermore, levels of immune checkpoint molecules on exosomes changed during and after therapy compared to baseline. Overall, plasma-derived exosomes have the potential as biomarkers for therapy monitoring in HNSCC patients.

Poster-PDF A-1380.PDF

Publication History

Article published online:
10 June 2020