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  Profiling of Immune Cells in Dog Cancer


   College of Medicine and Veterinary Medicine

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  Dr T Kitamura, Mr M Parys, Prof D Argyle  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Cancer represents a leading cause of mortality in dogs accounting for 30% of all deaths in the UK. Dogs with cancer are usually treated with surgery, radiation therapy, and/or chemotherapy to eliminate malignant cells. However, successful control of disease progression using these classical therapies is limited.

Immunotherapy is an emerging therapeutic approach for cancer that acts to boost the cancer-killing functions of cytotoxic T cells and has shown great promise in certain types of human cancer, in particular melanoma and lymphoma. However, its efficacy is limited to a fraction of patients likely due to accumulation of another type of immune cells such as tumour-associated macrophages (TAMs) that can suppress cytotoxic T cell function. It is needed to validate the status of cytotoxic T cells and TAMs in cancer in order to select dogs that are applicable for immunotherapy, and to evaluate and improve efficacy of therapy. However, characteristics of these cells in dog cancers are largely unknown.

We have recently established techniques to detect TAMs and cytotoxic T cells in canine cancers by flow cytometry and immunohistochemistry. In this study, we will investigate, 1) number and activation status of T cells in dog cancers, 2) characteristics of macrophages in there, and 3) correlations between the status of cytotoxic T cells and macrophages. We will mainly investigate melanoma and osteosarcoma, but also analyse B cell lymphoma. The tecniques to be used in this project are flow cytometry, immunostaining, RNA sequencing, and antibody development. This study will provide a basis to develop new diagnostic approaches for selection of dogs for immunotherapy, which may improve the life of canine patients suffering lethal cancers.

Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships


Funding Notes

3.5 year PhD
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

All applicants should also apply through the University's on-line application system for September 2020 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=826

References

1) Klingemann H (2018) Immunotherapy for Dogs: Running Behind Humans. Front. Immunol. 9:133.
2) Cassetta L, Kitamura T (2018) Macrophage targeting: opening new possibilities for cancer immunotherapy. Immunology. 155: 285-293.
3) Nirmal AJ, Regan T, Shih BB, Hume DA, Sims AH, Freeman TC. (2018) Immune Cell Gene Signatures for Profiling the Microenvironment of Solid Tumors. Cancer Immunol Res. 6: 1388-1400.

Where will I study?