Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. CD8+ T cells, IFNγ, and FasL, but not perforin, or TNFα were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthisis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1-/- mice and Fas defective lpr mice failed to eliminate intraocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras revealed that IFNγR1 and Fas expression on immune cells was most critical for rejection and SPLNX increased the frequency of activated macrophages (MΦs) within intraocular tumors in an IFNγ-and-Fas/FasL dependent manner suggesting an immune cell target of IFNγ and Fas. As depletion of MΦs limited CD8 T cell mediated rejection of intraocular tumors in SPLNX mice, our data support a model in which IFNγ-and-Fas/FasL dependent activation of intratumoral MΦs by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis, and suggests that immunosuppressive mechanisms which maintain ocular IP interfere with the interaction between CD8+ T cells and MΦs to limit immunosurveillance of intraocular tumors.
- Received May 13, 2014.
- Revision received September 5, 2014.
- Accepted September 14, 2014.
- Copyright © 2014, American Association for Cancer Research.