Neurofibromin 1 Impairs Natural Killer T-Cell-Dependent Antitumor Immunity against a T-Cell Lymphoma

• Published in: Frontiers in immunology 2018-01, Vol.8, p.1901-1901
• Main Authors: Liu, Jianyun, Gallo, Richard M, Khan, Masood A, Renukaradhya, Gourapura J, Brutkiewicz, Randy R
• Format: Article
• Language: English
• Subjects: antitumor immunity; CD1d; Immunology; natural killer T cells; neurofibromin 1; T-cell lymphoma
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2017.01901

Neurofibromin 1 (NF1) is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT) cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair) host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways. To study whether a haploinsufficiency in NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell population as well as the functional expression of CD1d in mice. mice were found to have similar levels of NKT cells as wildtype (WT) littermates. Interestingly, however, reduced CD1d expression was observed in mice compared with their WT littermates. When inoculated with a T-cell lymphoma mice survived longer than their WT littermates. Furthermore, blocking CD1d significantly enhanced antitumor activity in WT, but not in mice. In contrast, a deficiency in Type-I NKT cells increased antitumor activity in mice, but not in WT littermates. Therefore, these data suggest that normal NF1 expression impairs CD1d-mediated NKT-cell activation and antitumor activity against a T-cell lymphoma.