Enucleation-induced Metastasis of Intraocular Melanomas in Mice

The present review summarizes and integrates the results from recent studies on the metastatic behavior and immunology of intraocular melanomas in mice. The data suggest strongly that enucleation of a melanomacontaining eye promotes intravascular showering of melanoma emboli that, in the immunologically compromised host, develop into fulminant metastases. By contrast, similarly disseminated melanoma cells are rejected by T-cell-dependent immune mechanisms in the immunocompetent host. Preliminary results suggest that this immune rejection is mediated by cytotoxic T-lymphocytes. Several independent experiments showed that neither enucleation nor immune impairment alone is capable of inducing progressive metastases in the intraocular melanoma-bearing host. Thus, the development of progressive metastases from intraocular melanomas is a two step process requiring: (1) a surgeryinduced, intravascular showering of melanoma emboli and (2) a simultaneous impairment of T-cell-dependent immune functions. The present results support the Zimmerman-McLean hypothesis that enucleation of a melanoma-containing eye can (under defined conditions) promote the metastatic spread of the primary tumor. The finding that immunocompetent intraocular melanoma-bearing hosts reject disseminated metastases offers hope that immunotherapeutic maneuvers may greatly reduce the risk of metastatic disease.