Computational prediction of cell-cell interactions in the brain-tumour microenvironment

Sammanfattning: Glioblastoma is the fastest-growing, and the most common malignant brain tumour in adults. It is normally treated with surgery and radio- or chemotherapy, but the approximate life expectancy is of 15 months with a high probability of cancer recurring. Therefore, there is a need for decreasing its severity. Bulk and single-cell RNA sequencing allow the identification of cellular states in tumours affected by cell-intrinsic and extrinsic factors. Four different cellular states have been identified in glioblastoma: neural progenitor-like, oligodendrocyte progenitor-like, astrocyte-like, and mesenchymal-like. As glioblastoma is an immunosuppressive tumour, it can alter the immune system and increase the tumour's immune escaping by segregating immunosuppressive factors or interacting with the brain microenvironment.Two datasets were used in this study to explore if the localization of the tumour in the brain microenvironment and the tendency of glioblastomas to activate microglial cells are due to particular ligand-receptor interactions. Data quality control was applied to both datasets and SingleCellSignalR and CellphoneDB packages were used to predict the possible interactions. A total of seven experiments were designed for this study. The first dataset, GBmap, allowed us to do a comparison between tumour cells and microglia, tumour cells and other cell types in the brain, and the four cellular states of glioblastoma with microglia and macrophages. Next, healthy microglia from GBmap was used to compare with the tumour bulk data from the second dataset, HGCC. The bootstrap technique was performed to compare bulk data vs single-cell data, and a comparison between tumour cells and microglia or other cell types was analysed.Results showed specific and shared interactions between cell types or cellular states, revealing the different localization of the tumour cells depends on the expressed ligand-receptor pairs. Also, a total of four patterns of interactions were found in the 50 samples to have a different tendency to activate microglial cells, which are promising results to further explore drugs to interfere with or how these interactions are related to patient survival. Furthermore, even if glioblastoma is a heterogenous disease, more interactions were predicted with microglial/macrophage cells without a uniform pattern between patients, and therefore, this study is a starting point upon which further in vitro studies would be needed to study the predicted interactions as potential targets to stop the progression of this type of cancer.