Allogeneic tumors placed into the anterior chamber of the mouse eye grow progressively and disseminate freely to distant body sites. However, these disseminated tumor cells do not develop into fulminant metastases but are rejected by host immune processes. Further studies have shown that syngeneic introacular melanomas grow progressively but do not form metastases unless the tumor-bearing mouse is subjected simultaneously to enucleation and immune impairment (i.e., whole-body irradiation). Results from studies on various intraocular tumor models resemble the clinical situation in humans. Patients with intraocular melanomas appear to be able to control systemic metastases for long periods prior to surgical removal of the tumor. The intraocular melanoma model may be important in evaluating human intraocular melanoma patients whose neoplasms are treated with local radiation therapy. Intracameral transplantation of X-irradiated melanoma cells in mice elicits strong immunity against secondary tumor challenge. This finding suggests that in situ irradiation of human intraocular neoplasms not only reduces the tumor mass but also might have the additional benefit of eliciting protective immunity against secondary tumor formation.
The specific aims of the proposed research are to determine the effect of various forms of enucleation and mechanical ocular trauma in promoting the metastatic spread of primary intraocular neoplasms in mice. The mechanisms of immune resistance to a combination of in vitro and in vivo immunological assays. Adoptive transfer of various subsets of immune lymphocytes will be used to identify the specific immune elements that confer resistance to spontaneous metastases. In addition, mice subjected to selective immune impairment (i.e., B-cell-deficient, Ly 1+-deficient, and Ly2+-deficient mice) will be examined for their susceptibility to metastatic disease. Long term goals of this project are to gain a firm understanding of the immunological and non-immunological processes that either prevent or promote progressive metastatic tumor growth in hosts harboring intraocular neoplasms. Once these processes are characterized, immunotherapeutic strategies will be devised to augment crucial immune components and thereby reduce the risk of metastatic tumor formation in these hosts.
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