Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT

Marie Nicole Theodoraki, Saigopalakrishna Yerneni, William E. Gooding, James Ohr, David A. Clump, Julie E. Bauman, Robert L. Ferris, Theresa L. Whiteside

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Purpose: Exosomes, small extracellular vesicles (EVs) derived from the endocytic compartment of their parent cells, are present in plasma of cancer patients and may serve as non-invasive biomarkers of disease outcome. Here, we asked whether tumor-derived (TEX) and/or T-cell derived exosomes can predict outcome in head and neck squamous cell carcinoma (HNSCC) patients treated with oncological therapy. Materials and Methods: 18 HNSCC patients enrolled in phase I clinical trial and receiving a combination of cetuximab, ipilimumab and radiation therapy were serially monitored for TEX and T cell-derived exosomes. Exosomes isolated from plasma by size exclusion chromatography were fractionated into TEX and CD3 + T cell-derived exosomes by immunocapture. Exosome-associated proteins were quantified by on-bead flow cytometry. Exosome molecular cargos of patients whose tumors recurred within 2 years (N = 5) were compared to cargos of patients who remained disease free at 2 years (N = 13) after therapy. Results: The predictive value of the exosome molecular cargo for disease recurrence was evaluated pre-, during and post therapy. In patients whose disease recurred, total exosome proteins, TEX/total exosome ratios, total CD3+, CD3(-)PD-L1+ and CD3 + 15s+ (Treg-derived) exosomes increased from the baseline levels. In patients who remained disease free, total exosome protein and TEX levels decreased, CD3+ and CD3+ CD15s+ exosomes stabilized and CD3+ CTLA4+ exosomes declined after ipilimumab therapy. Conclusion: TEX and T cell-derived circulating exosomes instead of immune cells were used for monitoring of patients’ responses to oncological therapy. The results support the potential role of exosomes as a non-invasive tumor and immune cell biomarkers in cancer.

Original languageEnglish (US)
Article number1593805
JournalOncoImmunology
Volume8
Issue number7
DOIs
StatePublished - Jul 3 2019
Externally publishedYes

Keywords

  • Exosomes
  • T cell-derived exosomes
  • head and neck cancer
  • immunotherapy
  • tumor derived exosomes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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