Browsing by Subject "Eye Neoplasms"
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Item The Role of Interferon-Gamma, Cd4-Positive T Cells, and Cd8-Positive T Cells in the Immune Rejection of Intraocular Tumors(2007-05-22) Dace, Dru Samuel; Niederkorn, Jerry Y.Although the eye is an immune privileged site, intraocular tumors can sometimes be rejected by the immune system. Ad5E1 is an adenoviral gene-transformed tumor cell line that is rejected by the immune system when transplanted into the anterior chamber of the eye in syngeneic C57BL/6 mice. Two components of the immune system have been shown to be absolutely necessary for intraocular tumor rejection: CD4+ T cells and IFN-gamma , as mice deficient in these components cannot reject the tumor. This study further examined the role of IFN-gamma and CD4+ T cells in mediating rejection of intraocular Ad5E1 tumors, and examined the ancillary role of CD8+ T cells. IFN-gamma acted directly on Ad5E1 tumor cells and not host cells. The anti-tumor effects of IFN-gamma were multiple, as IFN-gamma induced tumor cell apoptosis and inhibited tumor cell proliferation. Also, IFN-gamma promoted tumor rejection by inhibiting angiogenesis, since IFN-gamma KO mice demonstrated increased tumor blood vessel density and IFN-gamma induced the up-regulation of 5 anti-angiogenic genes and the down-regulation of 4 pro-angiogenic genes in Ad5E1 tumor cells. CD4+ T cells infiltrated intraocular Ad5E1 tumors. Following rejection of Ad5E1 tumors in C57BL/6 mice, CD4+ T cells could be adoptively transferred to SCID mice and induce Ad5E1 tumor rejection. CD4+ T cell derived IFN-gamma might mediate tumor rejection, as these cells produce significant levels of IFN-gamma in response to Ad5E1 tumor antigens. Macrophages were necessary for CD4+ T cells to mediate rejection, as mice depleted of ocular macrophages developed progressively growing intraocular Ad5E1 tumors. CD8+ T cells were not required for rejection, as CD8+ T cell-depleted and CD8+ T cell KO mice rejected Ad5E1 tumors. However, CD8+ T cells infiltrated intraocular Ad5E1 tumors. Following rejection in C57BL/6 mice, CD8+ T cells could be adoptively transferred to SCID mice and protected them from Ad5E1 tumor growth, similar to the effect produced by adoptively transferred CD4+ T cells. In attempting to ascertain what CD8+ T cells utilize to mediate Ad5E1 tumor rejection, I determined that TNF-alpha was required for tumor rejection, but IFN-gamma , FasL, perforin, TRAIL and CTL activity were not necessary for CD8+ T cell-mediated tumor rejection.Item The Role of NKT Cells in Immune Evasion of Liver Metastases Arising from Intraocular Tumors(2014-03-27) Sadegh, Leila; Street, Nancy E.; Niederkorn, Jerry Y.; Brekken, Rolf A.; Ariizumi, Kiyoshi; McKenna, KyleUveal melanoma (UM) is the most common intraocular tumor in adults and liver metastasis is the leading cause of death in UM patients. We have previously shown that NKT cell-deficient mice develop significantly fewer liver metastases from intraocular melanomas than do wild-type (WT) mice. Here, we examine the interplay between liver NKT cells and NK cells in resistance to liver metastases from intraocular melanomas. NKT cell-deficient CD1d-/- mice and WT C57BL/6 mice treated with anti-CD1d antibody developed significantly fewer liver metastases than WT mice following either intraocular or intrasplenic injection of B16LS9 melanoma cells. The increased number of metastases in WT mice was associated with reduced liver NK cytotoxicity and decreased production of IFN-γ. However, liver NK cell-mediated cytotoxic activity was identical in non-tumor-bearing NKT cell-deficient mice and WT mice, indicating that liver metastases were crucial for the suppression of liver NK cells. Depressed liver NK cytotoxicity in WT mice was associated with production of IL-10 by bone marrow-derived liver cells and increased IL-10 receptor expression on liver NK cells. IL-10-/- mice had significantly fewer liver metastases than WT mice, but were not significantly different from NKT cell-deficient mice. Thus, development of melanoma liver metastases is associated with upregulation of IL-10 in the liver and an elevated expression of IL-10 receptor on liver NK cells. This impairment of liver NK activity is NKT cell-dependent and only occurs in hosts with melanoma liver metastases.Item [UT News](1986-11-14) Bosler, Tommy Joy