Using transcriptome analysis and gene expression sequencing, researchers have discovered that blood stem cells (HSPCs) cause increased cell division in glioblastoma tumours and suppress the immune system by producing large amounts of a transmembrane protein (PD-L1).
Glioblastomas are the most aggressive type of brain tumours and around 3 in 100,000 people develop them per year. Unfortunately, this form of cancer often persists after a combination of surgery, radiotherapy and chemotherapy. Following diagnosis, typical survival duration is about 15 months.
Immunotherapy is a type of treatment that aims to help the body’s immune system fight cancer cells. Immunotherapy drugs are more effective in some cancers than others, with the overall response rate estimated to be around 20%. However, the glioblastoma microenvironment is characteristically immunosuppressive compared to other malignancies. This means that immunotherapies show little effect on these brain tumours. The mechanisms behind these processes remain poorly understood.
Revealing blood stem cells
Recently, scientists at the German Cancer Consortium (DKTK) studied the microenvironment of glioblastomas to gain an understanding of how the immune system influences brain tumour progression.
Using a computational approach for transcriptome analysis, the team separated the signals of 43 different cell types, including 26 distinct immune cell types, from 217 glioblastomas. Surprisingly, this revealed that hematopoietic stem and precursor cells (HSPCs) were present in the tumour samples and that they were positively associated with glioblastoma malignancy and immunosuppression.
HSPCs are stem cells that are involved in a process called haematopoiesis. This is when HSPCs give rise to different types of blood cells in linages called myeloid or lymphoid. Myeloid cells are involved in the production of bone marrow – examples include macrophages and neutrophils. Lymphoid cells generate a type of white blood cell, called lymphocytes, which include T cells and B cells.
The role of HSPCSs in brain tumours had not been described previously. Therefore, to investigate the stem cells in more detail, 660 individual cells from fresh glioblastoma tissue were extracted and profiled using gene expression sequencing. It was found that HSPCs suppressed the immune system by producing large amounts of a transmembrane protein, called programmed death-ligand 1 (PD-L1). Furthermore, it was discovered that HSPCs increased the cell division of glioblastoma cells, promoting tumour growth.
Future studies of HSPCs
Identifying such an important element in the complex cellular landscape of glioblastomas is an important step towards revealing targets for brain tumour immunotherapies. In future clinical trials, analysis of HSPCs in fresh tissue biopsies may serve as a useful predictor of glioblastoma progression. Furthermore, exploration into the mechanisms behind tumour-associated HSPCs in more depth may lead to a potential treatment strategy that overcomes immunosuppression.
Igor Cima, a scientist at DKTK, explained: “We can now see an opportunity to intervene to modify the differentiation process of the glioma-associated blood stem cells, for example, through particular cell messengers. Hence, we could prevent the immune system from being blocked as a result of the tumour. Immunotherapies would then have a better chance of being effective against glioblastomas.”
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