Requirement of CD80 + costimulation for rejection of ocular tumors and termination of immune privilege

Abstract

Immune privilege in the anterior chamber of the eye is very effective at preventing elimination of ocular tumors that express weak tumor antigens. We previously demonstrated that DBA/2 mice immunized in the flank with a P815 tumor cell vaccine that expressed CD80/IL-12 was unable to terminate immune privilege and prevent tumor growth in the anterior chamber. In the present study, we determined whether expression of costimulatory signals on tumor cells injected via an ocular route would terminate immune privilege. We observed that CD80-positive tumors were always rejected from the anterior chamber. However, the pattern of tumor rejection was dramatically different depending upon whether the mice were either naïve, or immunized in flank against the tumor cells. Naïve mice that received an anterior chamber injection of CD80-positive tumors did not develop immune privilege and displayed strong delayed hypersensitivity (DH) against the tumor cells. Moreover, the ocular tumors were rejected by ischemic necrosis that induced atrophy of the eye and phthisis. When immunized mice received an identical injection of tumor cells in the anterior chamber, they also did not develop immune privilege and displayed strong DH. However, tumor rejection was considerably different and occurred without destruction of normal ocular tissue, or phthisis. To determine if immune privilege was restored in these eyes, mice received a second injection of P815 cells (CD80-negative) into the anterior chamber 2 weeks after the first CD80-positive tumors were eliminated. Surprisingly, immune privilege was not restored and the P815 tumors were eliminated completely, again without phthisis. We conclude that specific rejection of ocular tumors with minimal destruction of the eye requires systemic immunization and expression of CD80 costimulatory signals on tumors within the eye.