Role of Type I and Type II NKT cells in the host’s innate antitumor immune response to a B-cell lymphoma (50.26)

Abstract

Abstract 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 TCR [alpha] chain rearrangement and are called Type I NKT cells; all other NKT cells are Type II. In the current study, we have analyzed the roles for NKT cell subsets in the host’s innate antitumor response against the murine NS0 B-cell lymphoma model in vivo. As the NS0 cell line lacks detectable cell surface CD1d expression, murine CD1d1 cDNA or empty vector was transfected into NS0 cells to generate CD1d+ and control cell lines. 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 were predictive of tumor progression. Myeloid suppressor cells (CD11b+Gr1+) were present in larger numbers at the tumor site and in the spleen of tumor-bearing Type I NKT-deficient mice, suggesting a possible inhibition of antitumor immunosurveillance mediated by these cells. Therefore, 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 the immunotherapy of blood cancers. This study was supported by NIH grants RO1 CA89029 and AI46455 to RRB.[alpha]