Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma

• Published in: Blood Vol. 111; no. 12; pp. 5637 - 5645
• Main Authors: Renukaradhya, Gourapura J., Khan, Masood A., Vieira, Marcus, Du, Wenjun, Gervay-Hague, Jacquelyn, Brutkiewicz, Randy R.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-06-2008; The Americain Society of Hematology; American Society of Hematology
• Series: Immunobiology
• Subjects: Adoptive Transfer; Animals; Ascites - immunology; Biological and medical sciences; Cell Line, Tumor; Cytokines - metabolism; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunotherapy; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - mortality; Lymphoma, B-Cell - therapy; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Modulation of the immune response (stimulation, suppression); Myeloid Cells - immunology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Spleen - cytology; Spleen - immunology; Survival Rate; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Antineoplastic agent; Natural killer T cell; Rodentia; Natural immunity; Malignant hemopathy; Cellular immunity; B-Lymphocyte; Lymphoma; Immunological surveillance; In vivo; Vertebrata; Mammalia; Mouse; Lymphoproliferative syndrome; Animal; T-Lymphocyte; Humoral immunity; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-05-092866

Natural killer T (NKT) cells are a T-cell subpopulation known to possess immunoregulatory functions and recognize CD1d molecules. The majority of NKT cells express an invariant T-cell receptor (TCR) α chain rearrangement (Vα14Jα18 in mice; Vα24Jα18 in humans) and are called type I NKT cells; all other NKT cells are type II. In the current study, we have analyzed the roles for these NKT-cell subsets in the host’s innate antitumor response against a murine B-cell lymphoma model in vivo. In tumor-bearing mice, we found that type I NKT cells conferred protection in a CD1d-dependent manner, whereas type II NKT cells exhibited inhibitory activity. Pro- and anti-inflammatory cytokines secreted by splenocytes from tumor-bearing mice correlated with tumor progression. Myeloid cells (CD11b+Gr1+) were present in large numbers at the tumor site and in the spleen of tumor-bearing type I NKT–deficient mice, suggesting that antitumor immunosurveillance was inhibited by CD11b+Gr1+ cells. Overall, these data suggest that there are distinct roles for NKT-cell subsets in response to a B-cell lymphoma in vivo, pointing to potential novel targets to be exploited in immunotherapeutic approaches against blood cancers.