Anti-leukocyte function-1 antibody treatment prevents the rejection of intraocular regressor tumors and their metastases.
The role of the cell adhesion molecules, LFA-1 and ICAM-1, in intraocular tumor rejection was examined using four different syngeneic intraocular regressor tumors and four different inbred mouse strains. All four tumors undergo T cell-dependent immune rejection in the syngeneic host. Two of the tumors, D5.1G4 melanoma and P91 mastocytoma, undergo rejection by a cytotoxic T lymphocyte-like immune process. The other two tumors, UV5C25 fibrosarcoma and 124E2 melanoma, are rejected by a process that appears to be mediated by delayed-type hypersensitivity. Systemic administration of anti-LFA-1 prevented the rejection of all four categories of tumors. By contrast, similar in vivo treatment with anti-ICAM-1 antibody did not inhibit tumor rejection. The effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on the rejection of metastases arising from intraocular P91 tumors was also examined and found to be highly dependent upon normal LFA-1 function since antibody treatment with anti-LFA-1 prevented the rejection of metastases. Treatment with anti-ICAM-1 antibody alone had no appreciable effect on the rejection of metastases. The results from this study indicate that the expression and function of LFA-1 is crucial for the generation of immune responses to tumor antigens originating within the eye and the expression of tumor immunity within the eye and at distant sites.
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
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Li
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Mayhew
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Niederkorn
D000818:Animals; D000867:Anterior Chamber; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005134:Eye Neoplasms / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000276:immunology*; D013160:Splenic Neoplasms / Q000276:immunology / Q000556:secondary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1