The role of NKT cells in immune evasion of liver metastases arising from intraocular tumors (74.12)

Abstract

Abstract Uveal melanoma is the most common intraocular tumor in adults within the United States. Half of the patients develop liver metastases, which is almost universally fatal. We have previously demonstrated that liver natural killer (NK) cell-antitumor immunity was suppressed in mice bearing ocular tumors, and natural killer T (NKT) cells were responsible, in part, for liver NK cell suppression. This study examines the role NKT cells in promoting liver metastases arising from intraocular tumors. We showed that when wild type and NKT-deficient C57BL/6 mice were injected with B16LS9 melanoma cells, NKT-deficient mice developed less liver metastasis than wild type mice. The cytotoxicity of liver NK cells was also assessed. Results indicated that NK cells from NKT-deficient mice were more cytotoxic compared to NK cells from wild type mice. However, in-vitro assays suggested that NKT cells were unable to directly suppress NK cell-mediated cytotoxicity. To investigate the potential role of a third-party cell, myeloid derived suppressor cells (MDSCs) were depleted by anti-GR1 antibody. Surprisingly, tumor bearing MDSC-depleted mice developed more liver metastases than isotype-treated mice. Our results imply that liver NKT cells suppress NK cell cytotoxicity through a GR1+ third-party cell population other than MDSCs. We are currently investigating whether liver NKT cells impart their immunosuppressive function through GR1+ neutrophils.