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.
Keywords: NKT cells; CD1d; mouse models of lymphoma; mantle cell lymphoma; α-galactosylceramide
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Li, J.; Sun, W.; Subrahmanyam, P.B.; Page, C.; Younger, K.M.; Tiper, I.V.; Frieman, M.; Kimball, A.S.; Webb, T.J. NKT Cell Responses to B Cell Lymphoma. Med. Sci. 2014, 2, 82-97.
Li J, Sun W, Subrahmanyam PB, Page C, Younger KM, Tiper IV, Frieman M, Kimball AS, Webb TJ. NKT Cell Responses to B Cell Lymphoma. Medical Sciences. 2014; 2(2):82-97.
Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B.; Page, Carly; Younger, Kenisha M.; Tiper, Irina V.; Frieman, Matthew; Kimball, Amy S.; Webb, Tonya J. 2014. "NKT Cell Responses to B Cell Lymphoma." Med. Sci. 2, no. 2: 82-97.