Myeloid cell can suppress the immune response to tumor cells

For a long time, researchers had believed that the brain reduces inflammation by protecting itself from an aggressive immune response. But scientists from the University of Notre Dame have found that such an evolutionary control may work against it when a tumor cell tries to metastasize to the brain.

Myeloid cell can suppress the immune response to tumor cells
Research. Image Credit: Matt Cashore/University of Notre Dame.

In a study recently published in the Cell journal, scientists have demonstrated that one type of cell crucial for immunity, known as a myeloid cell, can inhibit the immune response—which has the effect of enabling breast cancer cells to spread to the brain to form secondary cancer cells there.

We wanted to understand how the brain immune environment responds to the tumor, and there are so many different cells, and so many changes. The traditional belief was that the process described in this paper would be anti-tumor, but in our case, after a lot of experimenting, we discovered it is a proponent of metastasis.”

Siyuan Zhang, Study Co-Author and Dee Associate Professor, Department of Biological Sciences, University of Notre Dame

Zhang is also a researcher at the Harper Cancer Research Institute.

Using an imaging method and single-cell sequencing, which was not sufficiently powerful even a few years back for this kind of work, the team found that microglia—a myeloid cell type—supported the outgrowth of breast cancer that has metastasized to the brain by the expression of many proteins.

To recruit more microglia to the metastasis, the microglia discharges one protein—an immune cell-attracting protein known as CXCL10. All these microglia express a protein called VISTA, which acts as protection against inflammation in the brain.

However, when faced with a cancer cell, the two-part process inhibited major T-cells. T-cells, which increase the immune response of the body, would generally inhibit the spread of cancer all through the body.

The stimulation of the VISTA checkpoint was not previously known as a promising promoter of brain metastasis, stated Ian Guldner, the study’s lead author and graduate student in Zhang’s laboratory.

Apart from using a mouse model for the study, the researchers utilized data mining methods to confirm the way humans’ brains would react.

Clinically, this is a relevant finding because antibodies have been designed that inhibited the VISTA protein in humans, added Guldner. But more significant studies need to be conducted to assure the safe, effective use of VISTA-blocking antibodies in individuals with brain metastases.

According to Zhang, learning about the structures inside the brain cells will allow scientists to interpret cancer and also understand degenerative diseases, like multiple sclerosis, Parkinson’s, and Alzheimer’s.

The brain immune system is a very active field, since brain cells are dysregulated during the aging process. There is so much to learn.”

Siyuan Zhang, Study Co-Author and Dee Associate Professor, Department of Biological Sciences, University of Notre Dame

Source:
Journal reference:

Guldner, I. H., et al. (2020) CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10. Cell. doi.org/10.1016/j.cell.2020.09.064.

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