Characterisation of Viral OncoProtein (VOP) and Tumor specific Protein (TSP) specific T cell responses in HPV virus associated Cervical and head-neck Cancers

Supervisors: Prof Tao Dong and Dr Yanchun Peng

T cells are known to fight infection within the body but they also work every day to clear cells with the potential to become cancerous. However, as a cancer develops it finds ingenious ways to evade detection and clearance by the immune system. Recent cancer therapies have focussed on highlighting cancer or targeting T cells to switch them back on and encourage targeted killing of tumour cells. These immunotherapies show promise, but many challenges remain including identification of appropriate tumour-associated antigens (TAA).

Our group has a wealth of experience in studying viral antigen specific T cell responses from Influenza virus, HIV and Hepatitis C virus infections. Most of which is as a result of our exclusive access to clinical cohorts for these diseases. Recently, we have become more interested in studying the functional capacity of cancer-specific T cells within the tumour microenvironment. We are looking at how these T cells are functionally deficient and trying to identify new targets for immunotherapy or cancer vaccine design. We have been aided in this by the generation of a strong collaboration with Prof. Ruozheng Wang, our joint T cell Immunology laboratory in China, and Xinjiang Cancer Hospital. This collaboration gives us access to large patient cohorts and fresh patient samples for analysis. Through this and the Oxford biobank, we have access to a wide range and high number of surgical samples. As a result of these efforts we have had several productive projects studying immune checkpoint T cell receptor expression in tumour infiltrating T cells (manuscripts in preparation).
We are currently focusing on two promising targets for immunotherapy: Viral OncoProtein (VOP) and Tumour Specific Protein (TSP) in virus-associated cancers such as Human Papillomavirus (HPV)- associated cervical and head & neck cancers, EBV-associated Nasopharyngeal Cancer and HBV-associated liver cancer. HPV-associated cancers have high rates of incidence and mortality worldwide. The aim of this D.Phil. project is to identify dominant T cell epitopes in HPV-associated cervical and head & neck cancers. We hope to identify key determinants for increasing anti-tumour T cell activity and controlling cancer development.

Training Opportunities
This project will be based in the MRC Human Immunology Unit at the Weatherall Institute of Molecular Medicine, with access to state-of-the-art facilities. The project provides an opportunity for training in a broad range of different techniques, such as cell culture, a range of cellular assays, flow cytometry, molecular biology, single cell analysis, CRISPR/CAS9 technology and bioinformatics analysis.
As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.

Publications

  1. Dong T. CD8+ cytotoxic T lymphocytes in human influenza virus infection. 2015 National science review 
  2. Rajapaksa US et al. HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation. 2012 PNAS 
  3. Wilkinson TM et al., Preexisting influenza-specific CD4 + T cells correlate with disease protection against influenza challenge in humans 2012. Nature Medicine 
  4. Zhang et al, Boosting human antigen-specific cytotoxic T-lymphocyte responses by genetic abrogation of immune checkpoints. 2017 submitted 
  5. Li et al, Applying CITRUS algorithm to flow cytometry data to reveal the distinctive expression of immune checkpoint receptors on peripheral T-and NK-cells in chronic HBV diseases. 2017 ms in preparation 
  6. Li et al, Analysis of immune checkpoint receptors on T cells indicates the regimen of mono-or combinatorial blockade immunotherapy in HBV associated HCC. 2017 ms in preparation

For further information please contact:  Prof Tao Dong