Abstract
Treatment of head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) often results in high-grade acute organ toxicity (HGAOT). As these adverse effects impair the patients' quality of life and the feasibility of the planned therapy, we sought to analyze immunological parameters in tumor material and blood samples obtained from 48 HNSCC patients in order to assess the potential to predict the individual acute organ toxicity. T cells in the tumor stroma were enriched in patients developing HGAOT whereas levels of soluble factors in the plasma and gene expression in whole blood did not coincide with the occurrence of acute organ toxicity. In contrast, the frequency and absolute numbers of selected leukocyte subpopulations measured in samples of peripheral blood mononuclear cells (PBMCs) directly before the beginning of CRT were significantly different in patients with HGAOT as compared to those without. When we validated several potential markers including the abundance of T cells in a small prospective study with 16 HNSCC patients, we were able to correctly predict acute organ toxicity in up to 81% of the patients. We conclude that analysis of PBMCs by fluorescence-activated cell sorting (FACS) might be a convenient strategy to identify patients at risk of developing HGAOT caused by CRT, which might allow to adapt the treatment regimen and possibly improve disease outcome.
Highlights
Treatment of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) consists of a multidisciplinary therapeutic approach including surgery and either radiotherapy (RT) or chemoradiotherapy (CRT) [1, 2]
We conclude that analysis of peripheral blood mononuclear cells (PBMCs) by fluorescence-activated cell sorting (FACS) might be a convenient strategy to identify patients at risk of developing high-grade acute organ toxicity (HGAOT) caused by CRT, which might allow to adapt the treatment regimen and possibly improve disease outcome
PBMC samples were stained with different combinations of monoclonal antibodies and analyzed by FACS to determine the percentages of T cells, B cells, NK cells and monocytes
Summary
Treatment of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) consists of a multidisciplinary therapeutic approach including surgery and either radiotherapy (RT) or chemoradiotherapy (CRT) [1, 2]. Patients with squamous cell carcinoma of the esophagus treated with RT showed an association of IL-2 and IFNγ serum levels with local tumor response [19]. Up to now only a few studies focused on therapy-associated side effects, such as the above-mentioned ones where pro-inflammatory cytokine levels were associated with an increased likelihood to develop HGAOT [19]. Since this analysis, did not refer to cytokine levels at the onset of therapy, its predictive value is limited
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