Understanding How Brain Tumor Cells Interact with the Immune System to Improve Patient Outcomes

The Basic Immunology Research Program studies the function of T cells in brain and spine cancers, in order to better understand the immunobiology of glioblastomas and improve immunotherapy.

By Neuro-Oncology Branch Staff

February 9, 2022


Neuro-oncology branch laboratory

In addition to surgery, radiotherapy, and chemotherapy, immunotherapy is now recognized as an effective treatment option for over 13 different cancer types. Unfortunately, glioblastoma is not one of them. However, researchers are hopeful that a better understanding of immunobiology in glioblastomas can improve the treatment efficacy of immune therapy.

Masaki Terabe, Ph.D., investigator at the NCI Center for Cancer Research's Neuro-Oncology Branch (NOB), leads this effort by heading the Basic Immunology Research Program. 

Dr. Terabe received his Ph.D. from the University of Tokyo in Japan in 1999, where he was trained as an immunologist studying parasitic infections. He subsequently came to NCI as a postdoctoral fellow in the Molecular Immunogenetics and Vaccine Section of the Metabolism Branch, which is now a part of the Vaccine Branch. There, he scaled the scientific ladder to become a senior associate scientist before joining the NOB as an investigator in 2019.

Thanks to his extensive knowledge of the immune system and chronic diseases, Dr. Terabe hopes to expand immunology research in cancer. “During my postdoc, I became very interested in this type of work and am still striving to understand how cancer cells are interacting with the immune system,” he says.

The Immune System and Cancer

While immunology is a very complex science, Dr. Terabe says that chronic diseases arise when the immune system fails to do its job to eradicate either a virus or abnormal cells.

“The immune system has a lot of mechanisms to prevent it from attacking itself. These are called immunoregulatory mechanisms,” he says. “However, cancer cells hijack this system and instead use it to stop the immune system from attacking them.”

Dr. Terabe uses this idea to fuel his research. His goal is to understand how exactly cancer cells evade the immune system, and what mechanisms they use for this counterattack.

Basic Immunology Program

The NOB’s Basic Immunology Research Program investigates various aspects of unconventional T cells. They focus on natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells—potent mediators of immune responses in brain and spine cancers. The Basic Immunology Research Program is studying the functions of unconventional T cells, as well as looking at the interaction between glioblastomas and NKT cells or MAIT cells.

Dr. Terabe and his team take multiple approaches, including bioinformatic analysis of patients’ samples, analysis of the interaction between human glioblastoma cell lines with human NKT cells, and analysis of unconventional T cells in syngeneic mouse glioblastoma models. All this research helps to better understand NKT cells in the context of brain cancer to create meaningful findings that lead to better patient outcomes. 

Two different types of immune cells can be found in glioblastoma tumor tissue. One type of cells is from the innate immune system, and the other is the cells from the adaptive immune system. There are certain cell types in the central nervous system that belong to the innate system, and these cells are known to be highly immunosuppressive and abundant in glioblastoma tumor tissue. On the other hand, the cells in the adaptive immune system contain a very limited number of effector T cells, which are needed to help the immune system respond appropriately.

Dr. Terabe and his team noticed that NKT cells and MAIT cells were missing from our understanding of the glioblastoma immune microenvironment. These cells bridge the gap between the innate and adaptive immune systems—and interact directly with the glioblastoma cells.

“NKT play critical roles in changing the mode of immune responses against cancer,” Dr. Terabe explains. “We know that if you manipulate NKT cells in the correct way, you can facilitate the anti-cancer immune response. If they get activated or if they're manipulated in a different direction, they can suppress anti-cancer immune responses.”

Dr. Terabe studies a vital research question in his lab: What is the function of these unconventional T cells in glioblastoma? He explains that these T cells quickly produce a large amount of cytokines upon activation (an essential part of the inflammatory process) and control the subsequent immune response.

The brain is the second most lipid-enriched tissue in the human body (following fat tissue). Glioblastomas have been shown to produce altered lipids, which are different from what the brain would normally produce. Dr. Terabe and his team wonder if these altered lipids can be recognized by NKT cells.

“The ultimate goal is to translate our laboratory discoveries to help patients with glioblastoma,” Dr. Terabe says.

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