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.
Li
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XY
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Mayhew
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E
Niederkorn
J Y
JY
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