Masaki Terabe, Ph.D.
Dr. Terabe’s research focuses on understanding the mechanisms of immune regulation, especially the roles of CD1d-restricted natural killer T (NKT) cells and other innate T cells. One of the major goals of his lab is to apply his discoveries to develop novel strategies of immune therapy for brain tumors. Dr. Terabe was the first to report the immunosuppressive function of type II NKT cells and has developed strategies to enhance cancer vaccine efficacy by targeting immunosuppressive pathways. He is an experienced immunologist and has been a part of multiple translational studies.
1) tumor immunology and immunotherapy, 2) vaccine, 3) translational research,
4) NKT cells and innate T cells, 5) brain cancer
Our research focuses on elucidating mechanisms regulating immune responses and applying the findings to develop strategies to make more effective immunotherapies and vaccines for brain cancer.
Immunotherapy is an emerging pillar of cancer modality. For example, checkpoint inhibitors (e.g., anti-CTLA4, anti-PD-1, anti-PD-L1) are now approved for the treatment of more than 10 different types of cancer, and their applications are expanding. However, brain cancer, especially glioblastoma multiforme (GBM) is one of the few cancer types that does not benefit from the current immunotherapies. This may be partly due to low mutation burden, an indication of a low number of tumor antigens that induces T cell-mediated immune response. Since checkpoint inhibitor treatment relies on pre-existing tumor-specific T cells in patients, for tumors with low mutation burden, it is necessary to actively induce tumor-specific T cell responses by providing tumor antigens to the immune system. Vaccines are a platform that provide the antigen. However, providing antigens is not sufficient to induce strong enough immune responses, and adjuvants that modulate immune responses and tissue environment should be combined.
A component that makes the brain unique compared to extra-cranial tissues is its enrichment of glycolipid content. Although conventional T cells recognize fragments of proteins, peptides, in the context of antigen presenting molecules such as class I MHC or class II MHC, CD1d-restricted NKT cells are a type of T cells that mainly recognize lipids including glycolipids in the context of a class Ib MHC molecule, CD1d. CD1d-restricted NKT cells regulate immune responses in multiple disease settings including cancer by producing a large amount of a variety of cytokines immediately after activation and by interacting with other immune cells such as innate cells. Thus, CD1d-restricted NKT cells can set the tone of subsequent immune responses. CD1d-restricted NKT cells can both facilitate and suppress tumor immunity dependent on the type of lipid antigen they recognize as well as the subset of NKT cells activated. We discovered that sulfatide-reactive type II CD1d-restricted NKT cells suppress tumor immunity and counteract type I (or invariant) CD1d-restricted NKT cells that facilitate tumor immunity. Since cancer cells frequently change the status of their lipid metabolism that can affect glycolipid composition of the cells, the altered lipids may change the activities of CD1d-restricted NKT cells. One of the aims of our research program is to understand the role of CD1d-NKT cells and their subsets in the regulation of tumor immunity against brain cancer. By using lipid antigens and lipid metabolism modulators, we also explore ways to manipulate functions of CD1d-restricted NKT cells to facilitate tumor immunity and apply the findings to enhance vaccine efficacy.
Selected Recent Publications
Possible Therapeutic Application of Targeting Type II Natural Killer T Cell-Mediated Suppression of Tumor Immunity.Front Immunol. 9: 314, 2018. [ Journal Article ]
- Curr Opin Immunol. 51: 111-122, 2018. [ Journal Article ]
Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy.Oncoimmunology. 6(5): e1308616, 2017. [ Journal Article ]
- Nature. 531(7593): 253-7, 2016. [ Journal Article ]
TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer.Oncoimmunology. 5(8): e1197459, 2016. [ Journal Article ]
Dr. Terabe received his Ph.D. degree working on immunopathology of leishmaniasis at University of Tokyo, Japan. He joined the Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, NCI in 1999 as a Visiting Fellow. He became a Research Fellow in 2002 and a Staff Scientist in 2005. In 2007, Dr. Terabe became an Associate Scientist and Deputy Section Chief of the Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, NCI. He became a Senior Associate Scientist in 2018. In 2019, Dr. Terabe joined the Neuro-Oncology Branch as a tenure-track investigator. His major interest is to understand immunoregulatory mechanisms.