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

J Transl Med. 2011 Oct 4;9:168. doi: 10.1186/1479-5876-9-168.

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.

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cell Membrane / metabolism
  • ErbB Receptors / metabolism*
  • Female
  • HLA-A2 Antigen / immunology
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Peptides / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • HLA-A2 Antigen
  • Peptides
  • EGFR protein, human
  • ErbB Receptors