Exploiting the immune response to halt progression of ocular melanoma

Purpose The purpose of this study was to characterize the requirements for spontaneous rejection of tumors transplanted in the anterior chamber (a.c.) of splenectomized mice as a first step toward identifying how to harness the immune reponses to eliminate intaocular tumors. Methods Luciferase expressing E.G7‐OVA (Luc E.G7) tumors were injected in the a.c. of the eye of wildtype, CD8 depleted, perforin deficient, IFNγ deficient, IFNγ receptor 1 deficient (IFNγR1), or inducible nitric oxide synthase (NOS2) deficient mice that were splenectomized or left untreated prior to tumor challenge. In some experiments intraocular macrophages were depleted by subconjunctival administration of clodronate liposomes. Luc E.G7 tumor growth was measured by bioluminescent imaging using an IVIS imager. Tumor‐specific OT‐I CD8+ T cells were monitored in vivo by flow cytometry. Results Luc‐E.G7 tumors grew progressively in the a.c. of nonsplenectomized mice but were spontaneously rejected in splenectomized mice. Rejection of ocular tumors in splenectomized mice required CD8+ T cells, macrophages, IFNγ and IFNγR1 expression by host cells. Infiltration of ocular tumors by CD8+ T cells and their expression of IFNγ were equivalent in splenectomized and nonsplenectomized mice. Perforin expression and nitric oxide production were not required for rejection of intraocular tumors. Conclusion These data suggest a model of ocular tumor regression in splenectomized mice in which CD8+ T cells express IFNγ to induce nitric oxide‐independent tumoricidal activity within intratumoral macrophages. Therefore, restoring tumoricidal activity in intratumoral macrophages is critical for CD8+ T cell mediated elimination of ocular tumors