[The expression of zeta-chain of the T cell receptor as prognostic marker for patients with head and neck cancer].
BACKGROUND
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 zeta-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 aggressiveness 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.


CONCLUSIONS
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 immunomodulation.
Müller
D
D
Hals-Nasen-Ohren-Klinik der Ludwig-Maximilians-Universität München, Klinikum Grosshadern, München.
Lang
S
S
Roskrow
M
M
Wollenberg
B
B
D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D005500:Follow-Up Studies; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis*; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D010039:Otorhinolaryngologic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D012086:Reoperation; D019139:Tumor Escape / Q000276:immunology
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain