Phenotypic and functional characterisation of regulatory T cells in head and neck squamous cell carcinoma

• Main Author: Drennan, Samantha
• Format: Dissertation
• Language: English
• Published: University of Hull and University of York 2013
• Subjects: Medicine

Head and neck cancer is the sixth most common cancer worldwide. Despite advances in therapy, the five year survival rate remains poor. The presence of regulatory T cells (Tregs) may be a mechanism by which head and neck squamous cell carcinoma (HNSCC) evades the immune system. Using flow cytometry to identify distinct Treg populations on the basis of phenotype and a CFSE proliferation assay, the frequency and suppressive activity of Treg populations from the peripheral circulation and tumour microenvironment of newly-presenting HNSCC patients was assessed. No difference in the circulating Treg prevalence was observed between HNSCC patients (n=39) and healthy controls (n=14), or between patients with HNSCC from different subsites. However, patients with advanced stage tumours and those with nodal involvement had significantly elevated levels of peripheral CD4+CD25highCD127low/- Tregs compared with patients who had early stage tumours (p=0.03) and those without nodal involvement (p=0.03) respectively. Circulating CD4+CD25highCD127low/- Tregs from the entire HNSCC patient cohort and patients whose tumours had metastasised to the lymph nodes suppressed 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, peripheral CD4+CD25interCD127low/- Tregs consistently induced greater suppressive activity than CD4+CD25highCD127low/- Tregs. The tumour microenvironment had an elevated frequency of Tregs (p≤0.002) and a lower frequency of effector T cells (p≤0.03) compared with the patient's peripheral circulation (n=15). No difference was observed in the level of suppression between tumour and peripheral Tregs. Using immunohistochemistry, patients with oropharyngeal tumours showed a significantly greater infiltration of Foxp3+ cells in the tumour and stroma compared with laryngeal tumours. Furthermore, as determined by ELISA, the dispersed tumour specimens secreted detectable levels of TGF-β and IL-10, but secretions from HNSCC (dissociated tumour samples and cell lines) did not influence the suppressive activity of Tregs. Clarifying the role of CD127low/- Tregs in HNSCC and the influence the tumour may have on the regulatory population will provide the opportunity, through future work, to establish whether Tregs can be used as a prognostic determinant or manipulated by immunotherapy.