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Immunological complicity in evolution of potentially malignant oral lesions

PGR-P-69

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Non-funded
Additional supervisors
Alisdair McKechnie, Josie Meade
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

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.<br />

<h2 class="heading hide-accessible">Full description</h2>

<p>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.</p> <p>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.</p> <h3>Aims and Objectives</h3> <p>This study will answer three questions:</p> <ol> <li>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?</li> <li>Can the alterations be used to predict the degree of epithelial dysplasia (mild, moderate or severe) and risk of progression to malignancy</li> <li>What are the effects of manipulation of the pathways in vitro?</li> </ol>

<h2 class="heading">How to apply</h2>

<p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School fmhgrad@leeds.ac.uk.</p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to fmhgrad@leeds.ac.uk</p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email fmhgrad to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: • British Council IELTS - score of 6.5 overall, with no element less than 6.0 • TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e: fmhgrad@leeds.ac.uk, t: +44 (0)113 343 8221.</p>