Gamma–delta T-cells in patients with squamous cell carcinoma of the head and neck

Abstract

In our attempt to characterize a general immune-suppression found in patients with squamous cell carcinoma of the head and neck (SCCHN) we now focused on a subset of CD3 lymphocytes described as gamma/delta-T-cells, a cell type with potential relevance in non-MHC restricted anti-tumor immune responses. Peripheral blood of 33 SCCHN patients and 33 age-matched controls (CON) was evaluated for the frequency of gamma/delta-T-cells among CD3+ T-cells and their onset of apoptosis (Annexin V binding) by multicolor flow cytometry. Results were correlated with clinical parameters. Patients with SCCHN had a significantly higher proportion of gamma/delta-T-cells compared to healthy controls (4.4+/-0.4% for SCCHN vs. 3.0+/-0.3% for CON, p=0.01). However, this increase was not paralleled with a difference in the onset of apoptosis if compared to CON. There was also no correlation between the proportion of gamma/delta-T-cells and tumor stage. However, a significantly higher proportion of gamma/delta-T-cells was found in patients with recurrent or metachronous second primary SCCHN (6.0+/-1.0%) if compared to the other SCCHN (3.8+/-0.4%, p=0.02). In a follow up 3-6 months post-treatment patients showed a decrease of gamma/delta-T-cells among CD3+cells (2.7+/-0.4%, n=4) if they were operated only and an increase if primary radio-chemotherapy (6.7+/-1.7%, n=8) or a combination of operation plus radio-chemotherapy (6.8+/-2.3%, n=3) was applied. Furthermore, patients receiving palliative treatment including radio-chemotherapy had highest values of gamma/delta-T-cells (9.1+/-2.7%, n=4) overall implicating that the treatment modality significantly influences the proportion of gamma/delta-T-cells. Since patients with SCCHN, particularly those with recurrent or second primary disease after treatment, had a higher proportion of gamma/delta-T-cells without signs of a reduced onset of apoptosis this could be due to an increased de novo generation. The current study implies that increased frequencies of gamma/delta-T-cells in patients with SCCHN may not only be the result of tumor-host interactions but the consequence of applied treatment modalities.