Dynamics of HMBG1 (High Mobility Group Box 1) during radiochemotherapy correlate with outcome of HNSCC patients

Strahlenther Onkol. 2022 Feb;198(2):194-200. doi: 10.1007/s00066-021-01860-8. Epub 2021 Oct 20.

Abstract

Purpose: High Mobility Group Box 1 (HMGB1) protein has been described as a consensus marker for immunogenic cell death (ICD) in cancer. To personalize treatments, there is a need for biomarkers to adapt dose prescription, concomitant chemotherapy, and follow-up in radiation oncology. Thus, we investigated the levels of HMGB1 in plasma of patients with head and neck squamous cell carcinoma (HNSCC) during the course of radiochemotherapy and follow-up in correlation with oncologic outcome and clinical confounders.

Methods: In our pilot study, 11 patients with advanced HNSCC were treated with definitive radiochemotherapy. Blood samples were taken weekly during treatment and frequently at follow-up visits. HMGB1 levels as well as routine laboratory values were measured and clinical information was collected including tumor volume, infections, toxicity, and follow-up data.

Results: In total, 85 samples were analyzed. In eight patients, HMGB1 levels (baseline vs. last available sample during treatment) were increasing and in three patients HMGB1 values were decreasing toward the end of treatment. All three patients with decreasing values developed tumor recurrence. By contrast, no relapse occurred in patients that showed increasing HMGB1 levels during therapy. Moreover, a positive correlation of HMGB1 levels with tumor volumes, C‑reactive protein (CRP) levels, infections, and grade three toxicity (RTOG) was observed.

Conclusion: HMGB1 might be a promising marker to monitor ICD in HNSCC during the course of radiochemotherapy. However, HMGB1 seems to reflect complex and diverse immunogenic responses and potential confounders. Infections and treatment-associated toxicity should be considered when interpreting the dynamics of HMGB1.

Keywords: Biomarker; Head and neck cancer; Immunogenic cell death; Plasma; Radiotherapy.

MeSH terms

  • Chemoradiotherapy
  • HMGB1 Protein*
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Neoplasm Recurrence, Local
  • Pilot Projects
  • Squamous Cell Carcinoma of Head and Neck / therapy

Substances

  • HMGB1 Protein
  • HMGB1 protein, human