NKT cell mediated responses to mantle cell lymphoma (48.35)

Abstract

Abstract Mantle cell lymphoma (MCL) is an aggressive subtype of Non-Hodgkin’s lymphoma that is characterized by the abnormal accumulation of CD20+CD5+ B cells in the lymph nodes, spleen, gastrointestinal tract, bone marrow and blood. Although treatment with combination chemotherapy can be effective, most patients relapse, and the outcome for MCL remains poor. Natural killer T (NKT) cells are important in regulating immune responses to tumors. The observation that lymphoma patients have a reduction in both NKT cell number and function suggests that the anti-tumor effects mediated by these cells may be compromised. In these studies, we have investigated NKT cell activation in response to MCL. We found that CD1d cell surface expression was highly variable in a panel of well-characterized MCL cell lines. Importantly, cell surface expression of CD1d did not directly correlate with the ability of the MCL lines to activate primary NKT cells. Circulating NKT cells in the peripheral blood of MCL patients were not stimulated by autologous B cells, even in the presence of the potent antigen, α-GalCer. However, when NKT cells from healthy donors were co-cultured with purified B cells from MCL patients, the NKT cells specifically recognized the malignant B cells and produced IFN-γ, but not inflammatory or regulatory cytokines. These data suggest that B cell lymphomas may condition autologous NKT cells not to recognize them in order to evade NKT cell mediated anti-tumor responses.