CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy

• Published in: Cancer Immunology, Immunotherapy Vol. 70; no. 5; pp. 1239 - 1254
• Main Authors: Hara, Ayaka, Koyama-Nasu, Ryo, Takami, Mariko, Toyoda, Takahide, Aoki, Takahiro, Ihara, Fumie, Kobayashi, Masayoshi, Hirono, Seiichiro, Matsutani, Tomoo, Nakayama, Toshinori, Iwadate, Yasuo, Motohashi, Shinichiro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2021; Springer Nature B.V
• Subjects: Aged; Animals; Antigen Presentation; Antigens, CD1d - metabolism; Antitumor agents; Brain cancer; Brain Neoplasms - immunology; Brain Neoplasms - therapy; Brain tumors; Cancer immunotherapy; Cancer Research; Cancer Vaccines - immunology; CD1d antigen; Cells, Cultured; Cytotoxicity; Cytotoxicity, Immunologic; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - immunology; Glioblastoma - therapy; Glioblastoma cells; Humans; Immunology; Immunotherapy; Immunotherapy, Adoptive - methods; Interleukin 2 receptors; Male; Medicine; Medicine & Public Health; Mice; Mice, SCID; Middle Aged; Natural killer cells; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; Natural Killer T-Cells - transplantation; Neoplasm Transplantation; Oncology; Original; Original Article; Retinoic acid; Tretinoin - metabolism; Xenografts; Stem-like cell; NKT cells; CD1d; Cancer immunotherapy; Retinoic acid; Glioblastoma
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-020-02742-1

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.