Natural killer (NK) cells are critical components of our immune system. The activating receptor NK cell lectin-like receptor gene 2D (NKG2D)-mediated immune recognition and the role of HLA-G, one of the non-classical MHC class I antigens have been recently highlighted in tumor immunology. We investigated the expression and localization of HLA-G, MICA, MICA/B, and ULBP-2 by immunohistochemistry and immunofluorescence anaysis in sections of orthotopic transplantation models of retinoblastoma. HLA-G and MICA/B were expressed in the cytoplasm of retinoblastoma cells and preferentially localized at the tumor periphery. In contrast, MICA and ULBP-2 were not expressed. Double immunofluorescence analysis together with Ki-67 revealed that HLA-G and MICA/B were primarily detected in a more proliferative area with high Ki-67 immunostaining, which implying that NKG2D ligand expression is somewhat correlated with the tumor cell proliferation. These results suggest that NKG2D ligands play a crucial role in immunomodulation in retinoblastoma and provide additional evidence that tumor-immune interactions play an essential role in retinoblatoma.
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NK cell-associated antigen expression in retinoblastoma animal model