Immunology of intraocular tumors

The immune surveillance hypothesis was introduced over 30 years ago and proposed that neoplasms express novel antigens that subjected them to immune detection and elimination. In order for immune surveillance to be effective in controlling neoplasms, two requirements must be satisfied: 1) the tumor must arise in a body site that permits the induction of the full array of immune responses and 2) the immune elements generated must have unfettered access to the tumor and be able to express their entire range of effector functions at the tumor site. The unique immunologic and anatomic features of the eye prevent the induction and expression of conventional immunity-a phenomenon known as 'immune privilege.' Although ocular immune privilege represents a theoretical obstacle to immune surveillance, some highly immunogenic intraocular tumors can circumvent immune privilege and undergo immune rejection. Uveal melanoma is the most common intraocular malignancy in adults, yet it occurs with a frequency that is no higher than neoplasms arising in conventional body sites. The presence of either tumor-infiltrating lymphocytes (TIL) or tumor-infiltrating macrophages (TIM) is associated with a poor prognosis in uveal melanoma patients and suggests that some immune responses to intraocular tumors might exacerbate, rather than mitigate, tumor progression. Although counterintuitive, this proposition is consistent with the 'immune stimulation' hypothesis of tumor progression offered by Richmond Prehn over thirty years ago. It remains to be ascertained if immune stimulation affects the malignancy of ocular tumors, but it represents an intriguing explanation for the paradoxes of uveal melanoma.