Myeloid cells can smother insusceptible reaction, advance cerebrum metastasis

Overview

• Post By : Kumar Jeetendra


• Source: University of Notre Dame


• Date: 28 Oct,2020

Scientists have long thought that the brain protects itself from an aggressive immune response to keep inflammation down. However, that evolutionary management may work against it when a cancer cell tries to spread to the brain, researchers at the University of Notre Dame have found.

In recently published research in the journal Cell, researchers showed that one type of cell important for immunity, called a myeloid cell, can suppress the immune response -; which has the effect of allowing breast cancer cells to metastasize to the brain to form secondary tumor cells .

“We wanted to know how the brain immune environment reacts to the tumor, and there are so many unique cells, so many changes,” said Siyuan Zhang, the Dee Associate Professor in the Department of Biological Sciences, a researcher for Harper Cancer Research Institute and a co-author on the newspaper. “The traditional belief was that the procedure described in this paper could be anti-tumor, but in our case, after a lot of experimentation, we discovered it’s a proponent of metastasis.”

During single-cell sequencing -; not powerful enough even a couple of years ago for this type of work -; and an imaging technique, the investigators found a myeloid cell type called microglia encouraged the outgrowth of breast cancer which has spread to the brain by the expression of many proteins. The microglia release one protein -; an immune cell-attracting protein called CXCL10 -; to recruit more microglia into the metastasis.

All these microglia express a protein named VISTA, which serves as protection against brain inflammation. But when faced with a cancer cell, this two-part process suppressed important T-cells. T-cells, which heighten the body’s immune response, would usually stop the spread of cancer throughout the body.

The activation of the VISTA checkpoint hadn’t previously been called a possible promoter of brain metastasis, said the paper’s lead author, Ian Guldner, a graduate student in Zhang’s laboratory. In addition to using a mouse model for the research, the team used data mining methods to validate how humans’ brains would react.

Clinically, the discovery is relevant, since antibodies have been developed that blocked VISTA in humans, Guldner stated. However, significant additional work has to be performed to ensure the safe and effective use of VISTA-blocking antibodies in people with brain metastases.

Learning about the structures inside cells in the brain will help researchers not only understand cancer, but also degenerative diseases such as Parkinson’s, multiple sclerosis and Alzheimer’s, Zhang said.

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, co-author on the paper