Abstract
Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.
Highlights
Non-Hodgkin’s lymphomas (NHL) are one of the few cancers of which incidence has increased over the past thirty years
It was unclear whether cellular alterations during malignant transformation could alter the lipid repertoire such that Natural killer T (NKT) cells would recognize B cell lymphomas
To determine if B cell lymphoma cells could directly induce NKT cell activation, we utilized a panel of murine B lymphoma cell lines
Summary
Non-Hodgkin’s lymphomas (NHL) are one of the few cancers of which incidence has increased over the past thirty years. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype; it is an aggressive lymphoma with heterogeneous clinical behaviors. DLBCL accounts for 25%–30% of NHL among adults in the United States and 60% of patients respond well to current therapy and have prolonged survival, the remainder succumb to the disease [1]. Another subtype of NHL, mantle cell lymphoma (MCL) is an aggressive disease that is characterized by the abnormal accumulation of. Treatment with combination chemotherapy can be effective, most patients relapse, and the outcome for MCL remains poor with a median survival of only five years [2,3,4].
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