Precision targeting of primary central nervous system lymphoma and its tumour microenvironment

原发性中枢神经系统淋巴瘤及其肿瘤微环境的精准靶向

• 批准号: MR/X001415/1
• 负责人: Keir Pickard
• 金额: $ 34.68万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX001415%2F1
• 关键词: Precision; targeting; primary; central; nervous

Primary central nervous system lymphoma (PCNSL) is lymphoma (immune cell cancer) confined to the brain. Compared with other types of lymphoma, the outlook is poor, with only 1 in 5 patients still alive 5 years after diagnosis. Relapse of the disease within the first 2 years after treatment is a common occurrence, and long-term survival following relapse is rare. There is a pressing need for new treatments for this condition which can reduce the risk of relapse without being too toxic for patients to tolerate.Here we propose to use single cell multi-omics (measuring RNA molecules inside cells and protein molecules on the surface of cells) to understand the behaviour of PCNSL cells and their interactions with surrounding immune and brain cells. To our knowledge this will be the first study of its kind to be performed in this disease area. Experiments performed will include measurements of gene activity and proteins expressed in the cancer and surrounding cells. This information could have broad and important implications for the management of PCNSL. By better understanding how the cancer cells behave and interact, we will be able to identify targets for new cancer treatments and combinations of treatments which could improve outcomes for patients.We will confirm our findings by looking at PCNSL cells within their tumour environment in archived diagnostic tissue samples, and we will compare with a genetically similar type of lymphoma (testicular lymphoma) within its distinct tumour environment.The research is being carried out in the Biosciences Institute at Newcastle University in collaboration with the Newcastle upon Tyne Hospitals NHS Foundation Trust. We will seek consent from patients to use excess tissue samples from brain biopsy at this single UK centre. These samples will be surplus to diagnostic requirements and so the study will not affect the diagnosis, treatment or care those patients receive in any way. Fully anonymised data from the study will be made publicly available for other researchers to explore, in line with policies of the publishers and the proposed funding bodies.

原发性中枢神经系统淋巴瘤（PCNSL）是局限于脑部的淋巴瘤（免疫细胞癌）。与其他类型的淋巴瘤相比，前景很差，只有1 / 5的患者在诊断后5年仍然存活。在治疗后的头2年内疾病复发是常见的，复发后的长期生存是罕见的。目前迫切需要新的治疗方法，既能降低复发的风险，又不会对患者造成无法忍受的毒性。在这里，我们建议使用单细胞多组学（测量细胞内的RNA分子和细胞表面的蛋白质分子）来了解PCNSL细胞的行为及其与周围免疫细胞和脑细胞的相互作用。据我们所知，这将是在该疾病领域进行的第一次此类研究。所进行的实验将包括测量基因活性和癌症及周围细胞中表达的蛋白质。这一信息可能对PCNSL的管理具有广泛而重要的意义。通过更好地了解癌细胞的行为和相互作用，我们将能够确定新的癌症治疗和治疗组合的目标，从而改善患者的预后。我们将通过在存档的诊断组织样本中观察肿瘤环境中的PCNSL细胞来证实我们的发现，并将与基因相似的淋巴瘤（睾丸淋巴瘤）在其不同的肿瘤环境中进行比较。这项研究是在纽卡斯尔大学生物科学研究所与纽卡斯尔泰恩医院NHS基金会信托合作进行的。我们将征求患者的同意，在这个单一的英国中心使用来自脑活检的多余组织样本。这些样本将超出诊断要求，因此研究不会以任何方式影响这些患者接受的诊断、治疗或护理。根据出版商和拟议资助机构的政策，该研究的完全匿名数据将公开供其他研究人员探索。