Influence of Immune Privilege on Ocular Tumor Development

Abstract

Mechanisms that maintain ocular immune privilege may contribute to ocular tumor progression by inhibiting tumoricidal immune responses. Consistent with that notion are observations from transplantable tumor models in mice demonstrating that the tumoricidal activity of CD8⁺ cytolytic T lymphocytes (CTL) may be inhibited directly by interfering with CTL effector function in the eye or indirectly by abrogating the effector function of CD8+ T cell-activated intratumoral macrophages that are critical for ocular tumor rejection. In addition, epigenetic gene regulation by factors within the ocular tumor environment favors the generation of tumor variants that are resistant to CD8⁺ CTL. Intratumoral macrophages may be essential for eliminating these variants because, unlike CTL, their tumoricidal activity is nonspecific. Hence, the inhibition of macrophage effector function within the eye, presumably to preserve immune privilege by minimizing ocular immunopathology, may hasten the outgrowth of tumor escape variants which contributes to ocular tumor progression.

KEYWORDS::

• immune privilege
• tumor
• epigenetic
• T cells
• macrophage
• CD8
• CTL

Declaration of interest: Supported by NE1 grants RO1 EYO18355 (KCM) and RO1 EYO1719804 (PWC), The Eye and Ear Foundation of Pittsburgh (KCM) and unrestricted grants from Research to Prevent blindness.