Macrophages in uveal melanoma and in experimental ocular tumor models: Friends or foes?

Macrophages belong to the innate immune system and as such constitute one of the first barriers against infection. They play an important role in wound healing, in inflammation and in angiogenesis, but are also essential in the first stage of a “danger response”. After scavenging debris, they can digest cellular proteins into smaller pieces, and protein-derived peptides can subsequently be presented to the immune system. Depending on the activation state of the macrophage, this antigen presentation may trigger a full-blown active immune response, or may suppress a potential immune reaction. Macrophages constitute a heterogeneous cell population described by many names, with varying phenotypic characteristics, depending on their tissue location and state of activation. They play important roles in different ocular tissues, including the cornea and the choroid, and have been found to be involved in anti-tumor immune responses in mouse ocular tumor models. One would thus expect macrophages to belong to the “good guys” that help to protect our body against dangers such as cancer. In human uveal melanoma however, a high density of macrophages is associated with a poor prognosis for the patient. Macrophages play a role in promoting angiogenesis, and thus may stimulate tumor growth; in addition, macrophages have also been found to suppress anti-melanoma immune responses. These functions may shift during aging. Taken together, these new observations extend our understanding of the diverse functions of macrophages and show us their different faces, making them either “friends or foes” in human uveal melanoma. A better understanding of these multifaceted cells will help in developing new treatments to prevent the growth of metastases in uveal melanoma patients.