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CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy
Ayaka Hara1,2, Ryo Koyama-Nasu3, Mariko Takami1
1Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Abstract:
Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients.
Insights
Invariant natural killer T (iNKT) cells show potential against glioblastoma. Targeting CD1d, an antigen-presenting molecule, on glioblastoma cells can enhance iNKT cell anti-tumor activity, offering a new immunotherapy approach.
Area of Science:
- Immunology
- Neuro-oncology
- Cancer Research
Background:
- Glioblastoma is an aggressive brain tumor with poor prognosis.
- Current treatments for glioblastoma are largely ineffective.
- Immunotherapy is a promising strategy for malignant brain tumors.
Purpose of the Study:
- To investigate the potential of invariant natural killer T (iNKT) cells in targeting glioblastoma.
- To assess CD1d expression on glioblastoma cells as a target for iNKT cell therapy.
Main Methods:
- Assessed CD1d expression on glioblastoma cells from patients.
- Evaluated iNKT cell-mediated cytotoxicity against CD1d-positive glioblastoma cells in vitro.
- Investigated the effect of retinoic acid on CD1d expression and iNKT cell activity.
- Administered human iNKT cells to orthotopic xenografts in mice to assess tumor regression.
Main Results:
- CD1d was expressed on glioblastoma cells from 10 of 15 patients.
- CD1d-positive glioblastoma cells induced iNKT cell-mediated cytotoxicity.
- Retinoic acid upregulated CD1d expression on glioblastoma stem-like cells, enhancing iNKT cell activity.
- Intracranial administration of iNKT cells led to tumor regression in a mouse model.
Conclusions:
- CD1d expression on glioblastoma cells is a viable target for immunotherapy.
- iNKT cells can exert anti-tumor activity against glioblastoma.
- CD1d-targeted NKT cell-based immunotherapy holds promise for glioblastoma treatment.
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