Die expression der ζ-kette des T-zell-rezeptors als prognosemarker bei kopf-hals-karzinomen

Introduction: The ζ-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 ζ-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 ζ-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), ζ-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 ζ-chain expression and the clinical aggressiveness of the tumor. Higher tumor stages frequently show a higher loss of the ζ-chain. In 11 patients ζ-chain expression of the PBL could be compared with TIL. Independent of the tumor stage the loss of the ζ-chain expression is much higher in TIL than in PBL. The loss of the ζ-chain expression also correlates with the progression of the disease. Patients with a high loss of the ζ-chain expression develop a recurrence more frequently. Conclusion: The loss of the ζ-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.