Researchers identify an immunotherapy target to combat glioblastomas

Antibodies positive for protein, S100A4 (in green) may be therapeutic targets to restore the antitumor activity of antibiotics to glioblastomas. Credit: Houston Methodist

Houston Methodist researchers have identified fingerprints of different genes and tumors of the head and immune system in glioblastoma, the worst and most common type of brain cancer in adults.

In-depth research of their more than 200,000 cells revealed a protein, called S100A4, that could be a therapeutic target for restoring antitumor activity. antibiotics to glioblastomas that degrade the immune system to protect it.

The study, entitled “A single study of human glioma and antibiotics found S100A4 as an immunosuppressive target,” was recently published in. Environmental communicationand continues to look for ways to treat cancer tumors, which include a wide variety of tumors and Normal cells mixed into a single mass. These rare cancers are difficult to control, because drugs that work with one group of tumors may be ineffective in others.

Nearly 48 percent of all primary brain diseases are glioblastomas, and more than 10,000 people in the United States become infected each year. Memory that is highly invasive cancer cells penetrating deep into the brain, performing surgery becomes a major challenge. A further complication of the disease is the fact that this cancer progresses rapidly, so even at different locations in a single patient’s brain, glioblastoma consists of a mosaic of a type of cancer, resulting in a large go back to the intended methods.

As in many brain diseases, the blood-brain barrier poses a challenge to drug delivery. In glioblastoma, the blood-brain barrier is weakened, allowing cells from surrounding to enter the central nervous system. Surprisingly, however, glioblastomas tend to selectively attract or convert most of the viruses that invade the virus into the immune system and promote their disease.

“Most antibiotics are currently intended to reactivate T cells, which are important for attacking and eliminating cancer cells, but in glioblastoma, T cell proliferation is much lower,” he said. Kyuson Yun, Ph.D. , a senior author on research with the Houston Methodist Studies Center and assistant professor of neurology at the Houston Methodist Institute. “Instead, there is an abundance of immunosuppressive myeloid cells in glioblastomas.”

To investigate the complex cancer-cancer interactions, the researchers conducted genetic data of different cell types in 44 samples of glioblastoma from 18 patients. For each patient, they examined the tissue of glioblastoma. from different parts of the tumor to gain an understanding of the type of cancer in each patient. Then, they processed a series of single-stranded RNA samples into individual cells based on their biological description of different pathogens.

After collecting cells based on their profiles, the researchers found that glioblastoma cells in and out of patients could be subdivided into nine groups based on their independent cell status and specific mutations in a single cell. They further identified nine different types of myeloid cells in glioblastoma, including the primary immune cells of the brain, microglia, which are associated with improved patient outcomes. Also, tumor tumors are filled with acquired macrophages of bone and bone marrow Tregs (Tregs) that are immune and associated with adverse patient outcomes.

Therefore, the researchers focused on identifying a virus that is active in the Tregs antibodies and myeloid cells. Their strategy is to isolate the “good” viruses that are associated with a healthy lifestyle and the selection of “bad” antibiotics that promote growth and avoid immunity. They found that the S100A4-activated protein was produced and secreted by glioblastoma cancer cells, immune T cells and vascular cells that originated in myeloid.

Yun said her team was planning to develop an antibiotic to deliver the S100A4 protein by glioblastoma that regulates T cells and macrophages found in bone. In addition, they plan to promote the growth of small cells that can penetrate the central nervous system and inhibit the activity of S100A4 protein in glioblastoma cells.

“Currently, therapists are taking the sledgehammer step since there has been a lack of understanding of what myeloid cells are promoting. glioblastoma growth and those that prevent it, says Yun. excess growth thus allowing us to take advantage of the option of controlling the immune system to restore normal functioning. immune system. “

She added that in the next few years the same genetic data as those in this study will significantly change the understanding of human cancer and lead efforts to develop new cancer drugs, especially antiretroviral drugs.

Innate immune landscape in glioblastoma cancer tumors

Learn more:
Nourhan Abdelfattah et al, Single-cell study of human glioma and antibiotics found S100A4 as an immunosuppressive target, Environmental communication (2022). DOI: 10.1038 / s41467-022-28372-y

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Houston Methodist

hintResearchers have identified an immunosuppressive target for the fight against glioblastomas (2022, April 5) returned 5 April 2022 from

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