T cell abundance in blood predicts acute organ toxicity in chemoradiotherapy for head and neck cancer
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L. Milena Beschel1,*, Martin Leu2,*, Sybille D. Reichardt1, Margret Rave-Fränk2, Markus A. Schirmer2,3, Christine Stadelmann4, Martin Canis5, Hendrik A. Wolff6,7, Holger M. Reichardt1,*
1Institute for Cellular and Molecular Immunology, University Medical Center, Georg-August-University Göttingen, Germany
2Department of Radiotherapy and Radiooncology, University Medical Center, Georg-August-University Göttingen, Germany
3Institute of Clinical Pharmacology, University Medical Center, Georg-August-University Göttingen, Germany
4Institute of Neuropathology, University Medical Center, Georg-August-University Göttingen, Germany
5Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center, Georg-August-University Göttingen, Germany
6University Medical Center, Georg-August-University Göttingen, Germany
7Present address: Strahlentherapie Radiologie München, Germany
*These authors share first and senior authorships
Holger Reichardt, email: [email protected]
Keywords: head and neck squamous cell carcinoma, acute organ toxicity, chemoradiotherapy, T cell, predictive marker
Received: June 04, 2016 Accepted: August 15, 2016 Published: August 29, 2016
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.
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