The effect of castrate levels of testosterone on the host immune system: overcoming the limits of immunotherapy in prostate cancer

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1) Scientific/Medical contestProstate cancer is the second cause of cancer death in males in the UK, accounting for around 12000 deaths every year, which means more than 30 men die because of prostate cancer every day. In just under half of the cases, prostate cancer is diagnosed when it has already spread in other parts of the body, especially bones. This means that cancer is now metastatic and it is impossible to radically remove the tumour surgically or with radiotherapy. In this case, the treatment aims to stop or slow down the cancer growth for as long as possible. Hormone therapies are one of the best treatment options for metastatic prostate cancer. These are effective treatments that can control the cancer for many years, but unfortunately in some patients the effect only last for few months, so different approaches are needed. Immunotherapy has been a game-changing treatment for many cancer types, but its efficacy in prostate cancer is limited. It is not clear if the use of hormone therapies changes the immune system so that it prevents the immunotherapy to be effective at least in a specific subgroup of prostate cancer patients.2) What is the research trying to achieve?With this project, we are trying to understand how treatments that block the production of testosterone, which is the main goal of hormone therapies in prostate cancer, alter the immune system. In particular, we want to characterize the several cell subtypes that form the immune system and observe changes in the composition before and after the starting of the treatment. 3) Why is this important?A better understanding on how hormone therapies and the immune system interact between each other will help us develop new treatment strategies involving immunotherapy in prostate cancer. All the clinical trials investigating immunotherapy in prostate cancer have given underwhelming results and in all of them immunotherapy was combined with hormone treatments. Our hypothesis is that we can increase the efficacy of immunotherapy by administering it prior to start hormone treatments.4) Who is carrying out the research?Dr Gianmarco Leone is a clinical research fellow at the UCL Cancer Institute and UCH Macmillan cancer centre in London. He completed his medical degree and oncology training in Italy. He then moved to London as part of the PRIME team. PRIME is an international study funded by AIRC and CRUK, that aims to develop tests to be performed on blood samples that can help monitor prostate cancer. This fellowship will be carried out under the supervision of Professors Gerhardt Attard, who is an internationally recognised scientist at the top of his field and an opinion leader in prostate cancer.5) How is the research to be conducted?This type of analysis is usually performed using tumour biopsies with the aim of studying the immune cells that stay closer to the tumour cells. However, to understand the changes of these cells, we require multiple biopsies from the same patient. This can be particularly stressful for our patients and increases the risk of complications, on top of being expensive and requiring lots of resources from the hospital side. In this project we are going to mainly use immune cells isolated from simple blood samples and we hope to prove that this method can be as informative as the former. We will compare the information obtained analysing immune cells isolated from tumour biopsies to the ones obtained from blood immune cells.