Increased frequency and suppressive activity of CD127low/− regulatory T cells in the peripheral circulation of patients with head and neck squamous cell carcinoma are associated with advanced stage and nodal involvement

Abstract

The presence of regulatory T (Treg) cells is thought to be an important mechanism by which head and neck squamous cell carcinoma (HNSCC) successfully evades the immune system. Using multicolour flow cytometry, the frequency and functional capacity of two CD4(+) CD127(low/-) Treg cell populations, separated on the basis of different levels of CD25 expression (CD25(inter) and CD25(high) ), from the peripheral circulation of newly presenting HNSCC patients were assessed with regard to clinicopathological features and healthy controls. The frequency of circulating Treg cells was similar between HNSCC patients and healthy controls, and for patients with HNSCC developing from different subsites (laryngeal compared with oropharyngeal). However, patients with advanced stage tumours and those with nodal involvement had significantly elevated levels of CD4(+) CD25(high) CD127(low/-) Treg cells compared with patients who had early stage tumours (P=0·03) and those without nodal involvement (P=0·03), respectively. CD4(+) CD25(high) CD127(low/-) Treg cells from the entire HNSCC patient cohort and from patients whose tumours had metastasized to the lymph nodes were also shown to suppress the proliferation of effector T cells significantly more, compared with those from healthy controls (P=0·04) or patients with no nodal involvement (P=0·04). Additionally, CD4(+) CD25(inter) CD127(low/-) Treg cells consistently induced greater suppressive activity than CD4(+) CD25(high) CD127(low/-) Treg cells on the proliferation of the effector T-cell populations (CD4(+) CD25(-) CD127(-/+) and CD4(+) CD25(+) CD127(+) ). Peripheral Treg cells, identified by the CD127(low/-) phenotype, have been shown to be influenced by a patient's tumour stage and/or nodal status in HNSCC; suggesting a role in tumour progression that could be manipulated by future immunotherapy.