Key points are not available for this paper at this time.
Although intraocular tumors reside in an immune-privileged site, they can circumvent immune privilege and undergo rejection, which typically follows one of two pathways. One pathway involves CD4(+) T cells, delayed-type hypersensitivity (DTH), and the culmination in ischemic necrosis of the tumor and phthisis (atrophy) of the eye. The second pathway is DTH-independent and does not inflict collateral injury to ocular tissues, and the eye is preserved. In this study, we used a well-characterized tumor, Ad5E1, to analyze the role of IFN-gamma in the nonphthisical form of intraocular tumor rejection. The results showed that IFN-gamma induced tumor cell apoptosis, inhibited tumor cell proliferation, and promoted rejection by inhibiting angiogenesis. Microarray analysis revealed that IFN-gamma induced up-regulation of five antiangiogenic genes and down-regulation of four proangiogenic genes in Ad5E1 tumor cells. Although IFN-gamma knockout (KO) mice have progressively growing intraocular tumors, IFN-gamma was not needed for the elimination of extraocular tumors, as all IFN-gamma KO mice rejected s.c. tumor inocula. This represents a heretofore unrecognized role for IFN-gamma in circumventing ocular immune privilege and eliminating intraocular tumors. The findings also reveal that some IFN-gamma-independent tumor rejection processes are excluded from the eye and may represent a new facet of ocular immune privilege.
Dace et al. (Tue,) studied this question.