Immunological complicity in evolution of potentially malignant oral lesions

Project description

Project Summary

Despite a number of innovative improvements in management of other cancers, survival rates of patients with oral cancer remain poor and unchanged in the last 4 decades. The majority of oral cancers arise in areas of long-standing epithelial dysplasia, yet an accurate means of predicting which dysplastic lesions will progress to malignancy remains elusive. Elucidation of the factors that determine whether dysplastic oral lesions will regress, persist or progress to malignant transformation may help guide clinical management strategies and allow development of chemo-preventive therapy.

The PD-1/B7 pathway plays a key role in regulation of immune responses. Variations in expression of the components of the pathway are implicated in T cell mediated immune disorders such as oral lichen planus, and also in the immunological anergy which characterises cancer. The pathway has been successfully manipulated in the clinical setting in order to stimulate effective anti-tumour immune responses, but the involvement of such pathways in oral premalignancy has not been investigated.

Immunological and inflammatory mechanisms have a complex relationship with carcinogenesis which is well illustrated by recent reports on immunotherapy of cancer. While PD-1 blockade was demonstrated to improve survival of patients with recurrent head and neck cancer, a potential side effect of PD-1 blockade for management of melanoma is a chronic oral graft-versus-host type reaction in which development of oral squamous cell carcinoma has been reported.

Aims and Objectives

This study will answer three questions:

1. Can alterations in immune checkpoint expression, such as the PD-1 pathway be demonstrated in lesions which are at risk of developing into oral cancer?
2. Can the alterations be used to predict the degree of epithelial dysplasia (mild, moderate or severe) and risk of progression to malignancy?
3. What are the effects of manipulation of the pathways in vitro?

Entry requirements

Please contact our staff for further details about entry requirements.

How to apply (email)

fmhgrad@leeds.ac.uk

How to apply (phone)

+44 (0)113 343 7497