Regulatory T cells and circulating cytokines : novel prognostic markers in squamous cells carcinoma of the head & neck

Al Hamarneh, Osama

October 2009

Thesis or dissertation

© 2009 Osama Al Hamarneh. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide and is considered a highly immunosuppressive tumour. Advances in the treatment modalities for HNSCC over the last 20 years involving surgery, radiotherapy, chemotherapy and immunotherapy are not fully reflected in increases in the 5 year survival rates, mainly due to locoregional recurrences and to a lesser extent, distant metastasis.

The role of anti-tumour immunity in relation to HNSCC has been intensely studied in the past few years. It is now becoming clear that the complex interaction between HNSCC and immune cells plays an important part in determining tumour growth and progression.

HNSCC patients were found to have an imbalance in Th1/Th2-type cytokines and elevated levels of CD4+CD25high Regulatory T cells (Treg). In this thesis, the circulating levels of serum IL10, IL12 and Treg cell levels in PBMC were determined and their association with clinical outcome in HNSCC patients were investigated.

Serum cytokine levels were determined by ELISA in patients pre-treatment (n=107), 4-6 weeks post-treatment (n=43) and in a cohort of non-tumour controls (n=40). Treg cell levels were determined by flow cytometry in these groups.

IL10 detectability was significantly higher in patients than controls. Pre-treatment IL10 levels in all anatomical sub sites, except oral cavity, were significantly elevated in stages III/IV, N+ patients and in T3/4 tumours. The detectability of IL10 significantly correlated with poorer survival after a maximum follow-up of 36 months. Treg cell levels were significantly higher pre-treatment in patients vs. controls, which did not change significantly 4-6 weeks post-treatment and did not correlate with any clinical parameters.

In conclusion, serum IL10 was found to be an independent factor in predicting a poor clinical outcome in newly-presenting tumours of laryngeal and pharyngeal origin. The role of circulating Treg cells as predictors of clinical outcome requires further investigation. Future work to correlate findings regarding IL10, IL12 and Treg cells in the peripheral circulation of HNSCC patients with their levels and function in tumour tissue and TIL is recommended.

Postgraduate Medical Institute, The University of Hull
Greenman, John (Professor of tumour immunology)
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