Zeta-Ketten Expression bei Patienten mit SCCHN und dendritische Zellen als Stimulatoren für T-Zellen In Vitro

Introduction The zeta-chain as an important component of the T cell receptor (TCR) is involved in the transduction of intracellular signals and is therefore critical for T cell activation and subsequent induction of an anti-tumor response. In patients with squamous cell carcinoma of the head and neck (SCCHN) several mechanisms of immune suppression have been described. The expression of the TCR -chain of both peripheral blood lymphocytes (PBLs) and tumor infiltrating lymphocytes (TILs) has been analysed in patients with SCCHN and correlated to clinical data. Methods TIL and PBL from 47 patients with SCCHN were obtained. To determine expression of the zeta-chain in both PBLs and TILs, double immunostaining with mAbs and flow cytometric analysis was performed. The technique combined an intracellular staining with a surface staining. Results As compared to healthy controls (n=23), zeta-chain expression was significantly reduced (p<0.002) in patients with SCCHN (n=23) with lowest expression in those with UICC VI disease. Our results show a tight correlation between the loss of zeta-chain-expression and the clinical aggresiveness of the tumor. Higher tumor stages frequently show a higher loss of the zeta-chain. In 11 patients zeta chain-expression of the PBL could be compared with TIL. Independent of the tumor stage the loss of the zeta chain-expression is much higher in TIL than in PBL. The loss of the zeta chain-expression also correlates with the progression of the disease. Patients with a high loss of the Zeta chain-expression develop a recurrence more frequently. Conclusion The loss of the zeta-chain documents a systemic immune defect, which even occurs in early tumor stages. Additionally to locoregional approaches future therapeutic strategies should also focus on systemic immunemodulation.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Ludwig-Maximilians-Universität

Year

2004

Author dc:creator

• Mueller, Daniel

Repository record source_url

https://edoc.ub.uni-muenchen.de/1769/

OAI identifier oai:identifier

oai:edoc.ub.uni-muenchen.de:1769