Article
EGFR peptide-specific T cells in head and neck squamous cell carcinoma
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Authors
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Patrick Schuler
- HNO-Universitaetsklinik, Essen, Germany
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Petra Boeckers
- Chirurgische Universitaetsklinik, Duesseldorf, Germany
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Rainer Engers
- Pathologische Universitaetsklinik, Duesseldorf, Germany
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Christian Arsov
- Urologische Universitaetsklinik, Duesseldorf, Germany
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Jens Greve
- HNO-Universitaetsklinik, Essen, Germany
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Stephan Lang
- HNO-Universitaetsklinik, Essen, Germany
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Henning Bier
- HNO-Klinik der Technischen Universitaet, Muenchen, Germany
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Theresa Whiteside
- Hillman Cancer Center, Pittsburgh, United States
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Thomas Hoffmann
- HNO-Universitaetsklinik, Essen, Germany
| Published: | July 6, 2010 |
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Outline
Text
In head and neck squamous cell carcinoma (HNSCC), expression of epidermal growth factor receptor (EGFR) correlates with poor prognosis and decreased survival rates. As the cellular immune response to EGFR expression in vivo remains unclear, the aim was to specify the frequency and function of EGFR-specific T cells in HNSCC patients.
Methods: The frequency of T cells specific for HLA-A2.1 restricted to EGFR derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined by corresponding tetramer/pentamer analysis in 18 HLA-A2.1+ HNSCC patients and 18 healthy HLA-A2.1+ individuals (NC). Patients’ results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific T cells was demonstrated by in vitro stimulation (IVS) with dendritic cells (DC) pulsed with the HLA-A2.1-restricted peptides.
Results: For both EGFR peptides the average frequency of specific CD8+ T cells (0.017% and 0.014%) was not significantly increased in the circulation of HNSCC patients compared to NC (0.019% and 0.014%). A large variability in the frequency of peptide-specific CD8+ T cells was found in HNSCC patients (0.002–0.076%) and NC (0.002–0.134%). All examined tumors showed EGFR expression. IVS with peptide-pulsed DC resulted in the expansion of EGFR-specific CD8+ T cells, which were reactive against the EGFR+ cell line UD-SCC 8 in IFN-γ ELISPOT. T cell expansion was significantly greater for the KLF-peptide than the YLN-peptide.
Conclusion: While EGFR peptide-specific T cells were present in the circulation of HNSCC patients, their mean frequency was not increased to that in NC. Patients showed variable frequencies of peptide-specific T cells. These T cells were responsive in vitro to stimulation with the relevant EGFR peptides (YLN and KLF) and recognized EGFR+ tumor cells. Strategies for expansion of EGFR-peptide specific CTL may be important for future immunotherapy of HNSCC patients.
Keywords: EGFR, head and neck carcinoma, tetramer, specific T cells
