Immune escape mechanisms of intraocular tumors

The notion that the immune system might control the growth of tumors was suggested over 100 years ago by the eminent microbiologist Paul Ehrlich. This concept was refined and expanded by Burnet and Thomas 50 years later with their articulation of the “immune surveillance” hypothesis. In its simplest form, the immune surveillance hypothesis suggests that neoplasms arise spontaneously and express novel antigens that are recognized by the immune system, which either eliminates the tumors or restrains their growth. Within the eye, immune responses are controlled and sometimes profoundly inhibited – a condition known as immune privilege. Immune privilege in the eye is the result of a complex array of anatomical, physiological, and immunoregulatory mechanisms that prevent the induction and expression of many immune responses. Tumors arising in the eye would seem to have an advantage in evading immune surveillance due to ocular immune privilege. Uveal melanoma, the most common and malignant intraocular tumor in adults, not only benefits from the immune privilege of the eye but also has adopted many of the mechanisms that contribute to ocular immune privilege as a strategy for protecting uveal melanoma cells once they leave the sanctuary of the eye and are disseminated systemically in the form of metastases. Although the immune system possesses a battery of effector mechanisms designed to rid the body of neoplasms, tumors are capable of rapidly evolving and countering even the most sophisticated immunological effector mechanisms. To date, tumors seem to be winning this arms race, but an increased understanding of these mechanisms should provide insights for designing immunotherapy that was envisioned over half a century ago, but has failed to materialize to date.