EGFR-specific T cell frequencies correlate with EGFR expression in head and neck squamous cell carcinoma

Autor: Ferris Robert L, Lehnerdt Goetz F, Dumitru Claudia A, Greve Jens, Bas Murat, Boelke Edwin, Engers Rainer, Boeckers Petra, Schuler Patrick J, Andrade Filho Pedro A, Brandau Sven, Lang Stephan, Whiteside Theresa L, Hoffmann Thomas K
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Journal of Translational Medicine, Vol 9, Iss 1, p 168 (2011)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/1479-5876-9-168
Popis: Abstract Background In head and neck squamous cell carcinoma (HNSCC), expression levels of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and decreased survival rates. As the mechanisms responsible for cellular immune response to EGFR in vivo remain unclear, the frequency and function of EGFR-specific cytotoxic T cells (CTL) was determined in HNSCC patients. Methods The frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry. Patients' results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation with dendritic cells pulsed with the peptides. Results Frequency of EGFR-specific CTL correlated significantly with EGFR expression in tumor sections (p = 0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells. Conclusion EGFR expressed on HNSCC cells induces a specific immune response in vivo. Strategies for expansion of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients.
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