Enucleation in consort with immunologic impairment promotes metastasis of intraocular melanomas in mice

A series of investigations was employed to determine if metastases of intraocular melanomas could be induced by experimental manipulations. Syngeneic B16F10 melanoma cells transplanted intracamerally into C57BL/6 mice produced progressively growing intraocular tumors, yet formed only occasional pulmonary metastases. Neither enucleation nor mechanical manipulation of the melanoma-containing eye promoted a significant increase in the incidence of metastases. Likewise, immunologic impairment in the form of natural killer cell deficiency, T-lymphocyte deficiency, or γ-irradiation-induced lymphopenia failed to produce spontaneous metastases in intraocular melanoma-bearing mice. However, enucleation in consort with immune impairment (T-cell deficiency) produced a sharp increase in the incidence and number of pulmonary metastases in intraocular melanoma-bearing mice. Further studies showed that external pressure to the tumor-containing globe (without enucleation) produced extensive metastases in athymic, nude mice. By contrast, atraumatic enucleation of rapidly frozen eyes prevented metastases of intraocular melanomas in similar hosts. Collectively, the results indicate that induction of distant metastases in hosts harboring intraocular melanomas requires two simultaneous processes: (1) mechanical manipulation of the melanoma-containing eye, and (2) concomitant impairment of T-cell-dependent immune processes. The data strongly suggest that mechanical manipulation of melanoma-containing eyes produced intravascular showers of melanoma cells that are rejected by T-cell-dependent immune processes in the immunocompetent host. In the absence of these normal T-cell-dependent immune mechanisms, enucleation-induced showers of blood-borne melanoma cells gain a foothold in the lung and form progressive metastases.