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.

Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

“…Consequently, ocular IP has become a subject of major recent interest, and its fundamental importance in inflammatory eye diseases is now widely accepted. [3][4][5][6][7][8][9][10][11][12][13][14][15] However, as every investigative ophthalmologist painfully experiences sooner or later, as a tissue on which to perform in vitro research, the human eye is an exceptionally rare commodity that is very difficult to come by. In the rare cases in which eyes are enucleated, the damage due to trauma, infection, or tumor growth raises questions as to how useful such tissue is in helping us to understand the physiology of human ocular IP.…”

Uveal Melanoma: The Inflammatory Microenvironment

“…The eye is an immune-privileged site, but inflammation can be present within the established ocular tumor microenvironment [6]. Inflammation was recently established as the seventh hallmark of cancer [7].…”

Long Overall Survival After Dendritic Cell Vaccination in Metastatic Uveal Melanoma Patients

“…The lack of proper immune surveillance in the eye can lead to characteristics that make tumor cells more susceptible for recognition by the immune system when cells disseminate systemically, for example, high expression of tumor-specific antigens, as well as less susceptible, for example, resistance to interferon-g-induced upregulation of major histocompatibility complex class II molecules. [36][37][38] At present, accumulating evidence shows that uveal melanoma tumor cells can be lysed by CD8þ T cells in vitro 39 and by T cells adoptively transferred in a mouse model, 40 indicating the susceptibility of uveal melanoma for immunotherapy.…”