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

Schuler PJ, Boeckers P, Engers R, Boelke E, Bas M, Greve J, Dumitru CA, Lehnerdt GF, Ferris RL, Andrade Filho PA, Brandau S, Lang S, Whiteside TL, Hoffmann TK - J Transl Med (2011)

Bottom Line: 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.EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Universität Duisburg-Essen, Hals-Nasen-Ohrenklinik Essen, Germany. patrick.schuler@uk-essen.de

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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Related in: MedlinePlus

Mean frequencies of CD8+ EGFR-specific T cells in HNSCC patients and healthy controls. Representative dot plots for tetramer staining are displayed (a). Results are displayed in percent (%) for the control staining with FLU- and HIV-specific tetramers, as well as the EGFR-specific pentamer KLF and tetramer YLN. For both EGFR-specific peptides, HNSCC patients with a high EGFR score (> 7) had a significantly elevated frequency of EGFR-specific CTL, compared to patients with low EGFR score (< 7) and normal donors (* p-value < 0.05). No significant difference was seen between normal donors and patients with low EGFR score (b).
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Figure 2: Mean frequencies of CD8+ EGFR-specific T cells in HNSCC patients and healthy controls. Representative dot plots for tetramer staining are displayed (a). Results are displayed in percent (%) for the control staining with FLU- and HIV-specific tetramers, as well as the EGFR-specific pentamer KLF and tetramer YLN. For both EGFR-specific peptides, HNSCC patients with a high EGFR score (> 7) had a significantly elevated frequency of EGFR-specific CTL, compared to patients with low EGFR score (< 7) and normal donors (* p-value < 0.05). No significant difference was seen between normal donors and patients with low EGFR score (b).

Mentions: In HNSCC patients with high EGFR score (> 7), the frequency of EGFR-specific CD8+ T cells was significantly (p < 0.05) increased for both peptides compared to NC and HNSCC patients with a low EGFR score (< 7) (Figure 2). Also, the frequencies of CTL for both peptides were correlated significantly in all individuals (r2 = 0.5). Patients' characteristics and frequencies of CTL are shown in Table 1. No correlation was found between EGFR-specific CTL frequency and TNM status or gender of the patients.


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

Schuler PJ, Boeckers P, Engers R, Boelke E, Bas M, Greve J, Dumitru CA, Lehnerdt GF, Ferris RL, Andrade Filho PA, Brandau S, Lang S, Whiteside TL, Hoffmann TK - J Transl Med (2011)

Mean frequencies of CD8+ EGFR-specific T cells in HNSCC patients and healthy controls. Representative dot plots for tetramer staining are displayed (a). Results are displayed in percent (%) for the control staining with FLU- and HIV-specific tetramers, as well as the EGFR-specific pentamer KLF and tetramer YLN. For both EGFR-specific peptides, HNSCC patients with a high EGFR score (> 7) had a significantly elevated frequency of EGFR-specific CTL, compared to patients with low EGFR score (< 7) and normal donors (* p-value < 0.05). No significant difference was seen between normal donors and patients with low EGFR score (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198929&req=5

Figure 2: Mean frequencies of CD8+ EGFR-specific T cells in HNSCC patients and healthy controls. Representative dot plots for tetramer staining are displayed (a). Results are displayed in percent (%) for the control staining with FLU- and HIV-specific tetramers, as well as the EGFR-specific pentamer KLF and tetramer YLN. For both EGFR-specific peptides, HNSCC patients with a high EGFR score (> 7) had a significantly elevated frequency of EGFR-specific CTL, compared to patients with low EGFR score (< 7) and normal donors (* p-value < 0.05). No significant difference was seen between normal donors and patients with low EGFR score (b).
Mentions: In HNSCC patients with high EGFR score (> 7), the frequency of EGFR-specific CD8+ T cells was significantly (p < 0.05) increased for both peptides compared to NC and HNSCC patients with a low EGFR score (< 7) (Figure 2). Also, the frequencies of CTL for both peptides were correlated significantly in all individuals (r2 = 0.5). Patients' characteristics and frequencies of CTL are shown in Table 1. No correlation was found between EGFR-specific CTL frequency and TNM status or gender of the patients.

Bottom Line: 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.EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Universität Duisburg-Essen, Hals-Nasen-Ohrenklinik Essen, Germany. patrick.schuler@uk-essen.de

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.

Show MeSH
Related in: MedlinePlus