Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer

Abstract

Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed antitumour immunity. The presence of CD4+CD25+ (T_reg) cells in these patients might be, in part, responsible for downregulation of antitumour immune responses. To evaluate the frequency and characteristics of T_reg in the peripheral circulation of patients with SCCHN, we used multicolour flow cytometry. Expression of CCR7, CD62L, ζ chain and Annexin V binding to T_reg and non-T_reg CD4+ lymphocyte populations were evaluated. T_reg were confirmed to be Foxp3+ and GITR+. The T_reg frequency was significantly elevated in patients with active disease and those with no evidence of disease (NED) following curative therapies. Both T_reg and non-T_reg CD4+ T cells in patients were significantly enriched in CCR7⁻ and CD62L⁻ cell subsets. Although T_reg in patients contained a higher proportion of double negative (CCR7⁻CD62L⁻) cells, the majority of T_regs were CCR7⁻CD62L+. The proportion of Annexin V+CD4+ T cells was higher in patients (Preg were significantly more sensitive to apoptosis than non-T_reg in patients and NC. Expression of ζ was reduced in all subsets of CD4+ T cells obtained from patients vs NC. The data suggest that T_reg in patients with SCCHN largely contain T cells with the ‘effector’ phenotype, which bind Annexin V and have low ζ expression, consistent with their activation state and a rapid turnover in the peripheral circulation.