Immunology and the Brain: Scientific Discoveries Needed to Improve Patient Outcomes

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

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. While different factors associated with glioblastoma have been attributed to the low effectiveness of immunotherapy, researchers are hopeful that a better understanding of immunobiology in glioblastoma can improve the treatment efficacy of immune therapy.

Masaki Terabe, Ph.D., Investigator at NCI’s Center for Cancer Research, Neuro-Oncology Branch (NOB) leads this effort with the Basic Immunology 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 be a Senior Associate Scientist before joining the NOB as an investigator in 2019. But it was during his graduate school studies that Dr. Terabe first became interested in T cell immunology, leading to his current research at the NOB.

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

The Immune System and Cancer

While immunology is a very complex science, Dr. Terabe simply explains that, in terms of chronic disease, 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,” says Dr. Terabe. “However, cancer cells hijack this system and instead use these built-in mechanisms to stop the immune system from attacking the cancer cells.”

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

Basic Immunology Program

The NOB’s Basic Immunology Program is focused on various aspects of unconventional T cells, such as NKT cells and MAIT cells, potent mediators of immune responses, in brain and spine cancers. The Basic Immunology Program is studying the functions of unconventional T cells and looking at the interaction between glioblastoma and NKT cells or MAIT cells.

To study this and more, Dr. Terabe and his team take multiple approaches, including bioinformatics analysis of patients’ samples, analysis of the interaction between human glioblastoma cell lines with human NKT cells, and analysis of the role 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, 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 there was a type of immune cell missing from the current understanding of the glioblastoma immune microenvironment, called unconventional T cells, more specifically, NKT cells and MAIT cells. These cells bridge the gap between the innate and adaptive immune systems and interact directly with the glioblastoma cells.

This is cutting edge science as not much is known about these types of T cells in brain cancer. “NKT cells have shown that they can play critical roles in changing the mode of immune responses against cancer,” explains Dr. Terabe. “We know that if you manipulate NKT cells in the correct way, you can facilitate the anti-cancer immune responses. 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 unconventional T cells in glioblastoma? He explains that unconventional 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 adipose tissue, which is fat). Glioblastoma has been shown to produce altered lipids, different from what the brain would normally produce. Dr. Terabe and his team then wonder if these altered lipids can be recognized by NKT cells as NKT cells recognize lipids as antigens abundant in the brain.

“The ultimate goal is to translate our laboratory findings of the immune system and glioblastoma to help patients in collaboration with the [NOB] Translational Immunology Program,” says Dr. Terabe.

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