Artikel
T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx
Suche in Medline nach
Autoren
-
Thomas Hoffmann
- Dept. of Otorhinolaryngology, University of Duesseldorf, Düsseldorf
-
Christian Arsov
- Dept. of Otorhinolaryngology, University of Duesseldorf, Düsseldorf
-
Theresa Whiteside
- Hillman Cancer Center, Piitsburgh, PA, USA
-
Peter Klussmann
- Dept. of Otorhinolaryngology, University of Cologne
-
Murat Bas
- Dept. of Otorhinolaryngology, University of Duesseldorf, Düsseldorf
-
Katrin Scheckenbach
- Dept. of Otorhinolaryngology, University of Duesseldorf, Düsseldorf
-
Vera Balz
- Dept. of Otorhinolaryngology, University of Duesseldorf, Düsseldorf
-
Henning Bier
- Dept. of Otorhinolaryngology, University of Duesseldorf, Düsseldorf
| Veröffentlicht: | 22. September 2005 |
|---|
Gliederung
Text
Immunization with tumor associated epitopes represents a novel therapeutic strategy for cancer patients. In previous studies we described T-cell responses against p53 epitopes in patients with head and neck cancer (Hoffmann et al. Cancer Res. 2002). In order to overcome obstacles associated with the use of the p53 “self-antigen” we are here focusing on immune responses against a viral antigen. Since squamous cell carcinoma of the oropharynx (SCCO) have been frequently described to be infected with oncogenic human papilloma virus (HPV) subtype 16 we were determined T-cell responses against HLA-A2.1 restricted HPV 16 E7 derived epitopes.
T cells of 20 HA-A2.1+ patients and 20 HLA-A2.1+ healthy individuals were evaluated by multicolor flow cytometry analysis using peptide-HLA-A2.1 complexes (tetramers) specific for 3 HPV 16 peptides E711-20, E782-90, E786-93. T cells specific for an influenza matrix peptide (a model recall antigen) or an HIV reverse transcriptase peptide (a model novel antigen) were studied in parallel. Obtained frequencies were compared with the HPV16 E7 and p16 status in tumor sections and in vitro stimulation experiments were performed with autologous dendritic cells as well as various target cells.
Patients with SCCO had higher frequencies of CD8+ T cells specific for 2 out of 3 HPV 16 E7 peptides if compared to those of normal donors. However, only for the E711-20 epitope a significant increase was detected for patients with tumors expressing HPV16 E7 (60%) and p16 (50%) compared to those with tumors negative for both markers.
Furthermore, HPV16 E711-20 and HPV16 E786-93 specific T-cells were expandable upon in vitro stimulation with peptide pulsed dendritic cells and were reactive against peptide pulsed targets as well as HPV16 E7 expressing CaSki.
The enumeration of T-cells specific for HPV16 E7 epitopes helps to characterize the interaction of the cellular immune system with SCCO infected with oncogenic HPV16 E7. In future, this may lead to the development of immunotherapeutical approaches comparable to those ongoing in HPV positive cervical carcinoma.
