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Targeting perivascular macrophages to enhance the efficacy of immunotherapy in prostate cancer


Project Description

Immunotherapies like checkpoint inhibitors do not work well in most prostate cancer patients, with only a small group showing durable responses. It is thought that this reflects the potent immunosuppression within the tumour microenvironment.

We recently identified a subset of CD206+ macrophages in prostate tumours that gather around blood vessels and inhibit the proliferation and activation of cytotoxic T cells (CTLs). Our latest data show that these cells express high levels of IL-10 and negative checkpoint regulators like PD-L1, PD-L2, TIM-3 and VISTA. These are known to inhibit various anti-tumour functions of CTLs in tumours.

The PhD student on this project will conduct experiments to see whether CD206-targeted nanoparticles (NPs) containing inhibitors for the above molecules stimulates tumour CTLs and prevent subsequent tumour growth. As we found recently that perivascular CD206+ macrophages are increased prostate tumours after a standard of care treatment for prostate cancer, androgen deprivation therapy (ADT), we will also see whether targeting these cells with NPs, prevents the development of resistance to ADT. The techniques to be used include: cell culture and transfection, immunofluorescence staining of mouse and human tissue sections, FACS, qPCR, synthesis and use of NPs, stats analysis of data, and preclinical models of primary and metastatic prostate tumours.

Funding Notes

Funding:
Self-funding

Entry Requirements:
Candidates must have an upper second class honours degree or equivalent overseas qualification, in a relevant subject.

References

Enquiries:
Interested candidates should in the first instance contact (Professor Claire Lewis, +44 (0)114 215 9012 & [email protected])

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select Oncology and Metabolism as the department.

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