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

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.

Plasma sICAM-1 correlates with tumor volume before primary radiochemotherapy of head and neck squamous cell carcinoma patients

“…sICAM-1 might be a soluble plasma marker for initial tumor burden. In contrast to cfDNA 39 and HMGB1 21 , sICAM-1 levels were not significantly influenced by infection or toxicity. As these con-FIGURE 3.…”

“…The patient cohort has been described previously in Clasen et al 21 Patients exhibited typical features for primary radiochemotherapy of HNSCC. Three female and eight male patients were included and the tumors were located in the oropharynx (n = 5), hypopharynx (n = 5) and larynx (n = 1).…”

“…No correlation of sICAM-1 levels with infection and toxicity were observed (in contrast to recent findings for HMGB1 in the same patient cohort). 21 The most prominent finding is a strong correlation of initial sICAM-1 concentrations with the tumor burden of the patients at the start of radiochemotherapy as contoured for radiotherapy planning. This finding is in line with a report on hepatocellular carcinoma, which also found a correlation of sICAM-1 levels with tumor volume and tumor stage.…”

“…As described previously 21 , eleven patients were included in this study, who underwent primary radiochemotherapy. Radiotherapy to 54 / 60 / 70 Gy to elective nodal regions / high risk regions / macroscopic primary tumor and lymph node metastases was combined with cisplatin in eight cases or 5-fluorouracil and mitomycin C in three patients, respectively.…”

Association of Cell Death Markers With Tumor Immune Cell Infiltrates After Chemo-Radiation in Cervical Cancer

“…A decreased expression of HMGB1 and increase expression of CRT was reported to be beneficial for the survival of patients with gliobastoma multiforme (42). On the other hand, HMGB1 levels were found to increase following chemoradiation only in patients with locally advanced head and neck squamous cell carcinoma who did not relapse, as opposed to the patients who relapsed (43). In patients with esophageal squamous cell carcinoma, HMGB1 was found to positively correlate with patient survival and was found upregulated in the tumor following preoperative chemoradiotherapy (29).…”