August 8, 2022

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Hematopoietic stem cells were first discovered in glioblastoma

Nat Commun: SHematopoietic stem cells were first discovered in glioblastoma

 

 

Hematopoietic stem cells were first discovered in glioblastoma.  In a new study, researchers from the German Cancer Center (DKTK) discovered hematopoietic stem cells in glioblastoma for the first time. These hematopoietic stem cells promote the division of cancer cells and at the same time suppress the immune response to this tumor.

This surprising discovery may provide new possibilities for the development of more effective immunotherapy against these malignant brain tumors. Related research results were recently published in the journal Nature Communications, with the title of the paper “Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression”.

Hematopoietic stem cells were first discovered in glioblastoma

 


Glioblastoma is one of the most aggressive brain tumors and the most common dangerous brain tumor in adults; they grow diffusely in healthy brain tissue, so it is almost impossible to completely remove it with surgery.

They ignore the combination of surgery, radiotherapy, and chemotherapy and usually continue to grow uncontrollably. Even immunotherapies that have been effective against other types of cancer in some cases have so far failed to treat these malignant brain tumors.

Co-author of the paper and Professor of Translational Oncology at the German Cancer Society Björn Scheffler explained, “Glioblastoma clearly creates an environment that actively suppresses the immune response.

They produce immunosuppressive messenger molecules, and in the immediate environment of the tumor, we find that certain types of immune cells specifically suppress immune defenses. “

Scientists did not know the details of the various immune cells in the microenvironment of glioblastoma.

However, Scheffler and his colleagues realized that in order to be able to use appropriate treatments to overcome tumor-related immunosuppression, it is necessary to have a precise understanding of the cellular composition of glioblastoma.

In 217 glioblastomas, 86 tissue samples from WHO grade II and III astrocytomas, and 17 healthy brain tissue samples, the authors used computer-assisted transcription analysis to draw the outline of the cell composition. These tissue samples were taken directly from the edge of the resection, where the remaining tumor cells and immune cells meet.

Hematopoietic stem cells were first discovered in glioblastoma
Use the transcriptome to estimate cell types. The picture is from Nature Communications, 2021, doi:10.1038/s41467-021-23995-z.

These authors were able to distinguish signals from 43 cell types, including 26 different types of immune cells.

To their great surprise, they found hematopoietic stem and precursor cells (HSPC) in all malignant tumor samples, while this cell type was not found in healthy tissue samples.

The paper’s co-author Celia Dobersalske said, “Hematopoietic stem cells actually exist in the bone marrow, and from there they provide the body with a variety of mature blood cells, apparently including all different types of immune cells. The hematopoietic stem cells of the brain tumor itself have never been seen before. Described.”

Even more surprising is that these hematopoietic stem cells seem to have lethal properties: they suppress the immune system and at the same time stimulate tumor growth.

When these authors cultured tumor-associated hematopoietic stem cells and glioblastoma cells in the same culture dish, cancer cell division increased. At the same time, a large number of PD-L1 molecules called “immune brake” are produced on the surface of these cancer cells.

Tumor organoids-tiny tumors from individual patients’ brain tumor cells grown in petri dishes-also respond to hematopoietic stem cells. In the presence of these stem cells, cancer cells form a network of cell protrusions that connect them.

Only a few years ago, scientists from the German Cancer Research Center and Heidelberg University Hospital had discovered that glioblastoma cells use these connections to communicate, thereby protecting themselves from treatment-related damage.

All these observations indicate that the hematopoietic stem cells found in glioblastoma have a negative impact on the development of the disease. A previous study of 159 patients with glioblastoma whose clinical course is available has confirmed this.

In this group of patients, it can be observed that the more hematopoietic stem cells contained in this tumor, the more immunosuppressive messenger molecules released, and the more immunosuppressive markers formed by cancer cells — the overall survival of the patient The lower the rate.

To study hematopoietic stem cells in brain tumors in more detail, the authors extracted individual cells from fresh patient tissues.

They sequenced the gene expression of 660 cells, built relevant maps, and compared them with cells from healthy bone marrow and blood.

The analysis of these data puts forward several specific new suggestions, namely how to make this cell population that promotes tumor growth harmless.


It has been known from previous research reports that hematopoietic stem cells in bone marrow tend to mature into immunosuppressive cell types during the differentiation process of cancer.

They seem to be controlled by tumors. Igor Cima, the corresponding author of the paper, speculated that similar phenomena may also exist in glioblastoma-related hematopoietic stem cells: “We can now see an opportunity for intervention to change the differentiation process of glioma-related hematopoietic stem cells, for example, through Specific cell messenger molecules to prevent the immune system from being suppressed by tumors. Then, immunotherapy will have a better chance of being effective against glioblastoma.”

 

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