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

原发性中枢神经系统淋巴瘤(PCNSL)是一种局限于大脑的淋巴瘤(免疫细胞癌)。与其他类型的淋巴瘤相比，前景不佳，仅1/5的患者在确诊后5年内仍能存活。该病在治疗后头两年内复发是很常见的，复发后长期存活的情况很少见。迫切需要新的治疗方法来治疗这种疾病，既可以降低复发的风险，又不会对患者产生太大的毒性，患者无法耐受。在此，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，这将是在这一疾病领域进行的第一次此类研究。进行的实验将包括测量癌症和周围细胞中的基因活性和表达的蛋白质。这些信息可能会对PCNSL的管理产生广泛而重要的影响。通过更好地了解癌细胞的行为和相互作用，我们将能够为新的癌症治疗方法和治疗组合确定目标，从而改善患者的预后。我们将通过观察存档诊断组织样本中肿瘤环境中的PCNSL细胞来证实我们的发现，并将在其独特的肿瘤环境中与基因相似的淋巴瘤(睾丸淋巴瘤)进行比较。这项研究正在纽卡斯尔大学生物科学研究所与纽卡斯尔泰恩医院NHS基金会的合作下进行。我们将寻求患者的同意，使用来自英国这个单一中心的大脑活检的多余组织样本。这些样本将超出诊断要求，因此这项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。根据出版商和拟议的资助机构的政策，这项研究的完全匿名数据将公开提供给其他研究人员探索。

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.