Can changes in lifestyle that modify the immune system slow the progression of prostate cancer?

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Jeff Holly, Claire Perks, Nic Timpson, Amit Bahl


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Rationale

In many men prostate cancer is not life-threatening but in a few the disease progresses rapidly with few treatment options and as a consequence poor prognosis. The prevalence of, and mortality from, prostate cancer is much lower in many parts of the world, and epidemiological studies indicate that this is due to effects of lifestyle on the progression of the cancer. There has been a recent breakthrough in the development of cancer immunotherapy’s with dramatic results in clinical trials. These therapies target the way in which tumour cells avoid the immune system by upregulating immune checkpoint molecules. The most studied of these being programmed cell death (PD)-1, which is activated by the ligands PD-L1 and PD-L2 that are produced by tumour cells enabling them to escape immuno-surveillance. It is well known that the immune system is affected by lifestyle but it is not known whether such effects on the immune system contribute to the effects of lifestyle on cancer progression.

Aims & objectives

A cross-disciplinary project that will use prostate cancer cell lines to examine whether lifestyle-related metabolic disturbances affect the secretion of immune-system regulators. and large cohorts of men to examine whether these immune regulators differ according to lifestyle. In addition men with prostate cancer will be examined to see whether there are associations between the natural genetic variations in metabolic and immune-regulators and disease progression.

Methods

A range of prostate cancer cell lines will be employed to examine the regulation of immune-system regulators. Cell growth, metabolism, differentiation status, invasion and migration will be examined using established assays. PCR and immunoassays and western blotting will be used to monitor abundance of mRNA and protein respectively. Associations between genetic and epigenetic variants in immune-system regulators and associated pathways will be examined in large cohorts of men and in data from the UK Biobank in relation to the risk and progression of prostate cancer.

References


Created on Dec. 16, 2016, 11:09 a.m.