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

1)前列腺癌是英国男性癌症死亡的第二大原因，每年约有12000人死亡，这意味着每天有30多名男性死于前列腺癌。在不到一半的情况下，前列腺癌是在它已经扩散到身体其他部位，特别是骨骼时被诊断出来的。这意味着癌症现在是转移性的，不可能通过手术或放射治疗从根本上切除肿瘤。在这种情况下，治疗的目的是尽可能长时间地阻止或减缓癌症的生长。激素疗法是转移性前列腺癌的最佳治疗选择之一。这些都是有效的治疗方法，可以控制癌症多年，但不幸的是，在一些患者中，效果只能持续几个月，因此需要不同的方法。免疫疗法已经成为许多癌症类型的改变游戏规则的治疗方法，但其在前列腺癌中的疗效有限。目前尚不清楚激素疗法的使用是否会改变免疫系统，从而阻止免疫疗法至少在特定的前列腺癌患者亚组中有效。2）这项研究试图实现什么？通过这个项目，我们试图了解阻断睾丸激素产生的治疗方法如何改变免疫系统，睾丸激素是前列腺癌激素治疗的主要目标。特别是，我们希望表征形成免疫系统的几种细胞亚型，并观察治疗开始前后组成的变化。3)为什么这很重要？更好地了解激素疗法和免疫系统如何相互作用，将有助于我们开发涉及前列腺癌免疫疗法的新治疗策略。所有研究前列腺癌免疫疗法的临床试验都没有给人留下深刻的印象，所有这些试验都将免疫疗法与激素治疗相结合。我们的假设是，我们可以通过在开始激素治疗之前进行免疫治疗来提高免疫治疗的疗效。4）谁在进行这项研究？Gianmarco Leone博士是伦敦UCL癌症研究所和UCH Macmillan癌症中心的临床研究员。他在意大利完成了医学学位和肿瘤学培训。然后他搬到了伦敦，成为PRIME团队的一员。PRIME是一项由AIRC和CRUK资助的国际研究，旨在开发对血液样本进行的测试，以帮助监测前列腺癌。这项研究将在格哈特阿塔德教授的监督下进行，他是国际公认的前列腺癌领域的顶尖科学家和意见领袖。5）如何进行研究？这种类型的分析通常使用肿瘤活检进行，目的是研究与肿瘤细胞更接近的免疫细胞。然而，为了了解这些细胞的变化，我们需要从同一个病人身上进行多次活检。这对我们的病人来说特别有压力，增加了并发症的风险，而且价格昂贵，需要医院方面的大量资源。在这个项目中，我们将主要使用从简单血液样本中分离的免疫细胞，我们希望证明这种方法可以像前者一样提供信息。我们将比较分析从肿瘤活检中分离的免疫细胞和从血液免疫细胞中获得的信息。

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.