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

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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.