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Identification of key determinants affecting the quality of human Cancer specific cytotoxic T cells


Weatherall Institute of Molecular Medicine

Friday, January 08, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

The main objective of my group’s research is to focus on the functional aspects of the antigen specific T cells and study the factors affecting Cytotoxic T cells in controlling cancer development.

Cancer individuals are characterized by dysfunctional anti-tumor T-cell responses. In recent years, multiple inhibitory receptors, known as immune checkpoint receptors, expressed on T cells, have been identified. Recent exiting results from clinical trials with antibodies targeting these inhibitory receptors, such as PD-1 and CTLA4, have demonstrated their ability to activate anti-tumour immunity in a broad range of cancer patients, with dramatic therapeutic results. However only a small proportion of the patients responded to currently available immune-checkpoint blockade therapy. One of the main aims of our group is to explore the potential targets for immunotherapy which could improve the efficacy of current immunotherapeutic strategies, several ex vivo and in vitro T cell platforms with most advanced technologies (such as CyTOF, single cell RNASeq with 10X Genomics and SmartSeq 2) have been set up and optimised in our group. These cutting edge platforms enabled us to characterise Cancer-specific T cells isolated from cancer patients, to understand the correlation between “dysfunctional” T cell responses and ineffective control of cancer cells, and to identify key determinants affecting the quality of human Cancer-specific cytotoxic T cells.

We have performed single cell analysis with specific subsets of T cells isolated from cancer tissues and have identified unique molecular signatures in clonal expanded cell subsets. This D.Phil project will be focused on evaluating the potential of these newly identified molecules as target for future immunotherapy.

The student will be mentored by Professor Tao Dong and Dr. Yanchun Peng. The student will receive formal training in flow cytometry, cell culture, T cell cloning, full range of assays to evaluate T cell function , T cell receptor repertoire analysis , CyTOF, RNASeq and bioinformatics.

Students will be enrolled on the MRC WIMM DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

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.

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.

All WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.




Funding Notes

Funding for this project is available to scientists through the WIMM Prize Studentship and the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.

For October 2021 entry, the application deadline is 8th January 2021 at 12 noon midday, UK time.

Please visit our website for more information on how to apply.


References

1. ABD HAMID M Et al , Efficient anti-tumor effector responses by metabolically energetic CD103+ T cells with accelerated T cell apoptosis, under revision for Cancer Immunology Research. (Ms available upon request)
2. LI, X ET AL, A comprehensive analysis of key immune checkpoint receptors on tumor infiltrating T cells with implication of anti-cancer immune therapy REVISION SUBMITTED TO FRONTIERS ONCOLOGY. (Ms available upon request)
3. ABD HAMID M Et al, 2019. Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses. Cancer Immunol Res, 7(8), pp. 1293-1306.
4. Hang C, et al 2018 Et al, Genetic abrogation of immune checkpoints in antigen-specific cytotoxic T-lymphocyte as a potential alternative to blockade immunotherapy. Sci Rep, 8 (1), pp. 5549.
5. LEE LY-H ET AL, Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals 2008, J Clin Invest, 118 (10), pp. 3478-3490.

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