Termination of systemic immunity in the presence of intraocular tumors: influence of ocular immune privilege on tumor vaccines.
Ocular immune privilege preserves the visual axis by preventing the induction of sight-threatening nonspecific inflammation. Although privilege is essential for maintaining visual integrity, intraocular tumors exploit the privileged environment and grow progressively within the anterior chamber of the eye. Recently, a large number of laboratories have constructed genetically engineered tumor cell vaccines that express high levels of costimulatory signals. These vaccines are designed to bypass the normal pathways of T-cell activation and directly activate CD8+ tumor-specific T cells. In the following series of experiments, we determined whether a tumor cell vaccine that uses costimulatory signals (CD80 and IL-12) is capable of eliminating tumors within the immune-privileged anterior chamber. As expected, vaccine-immunized mice rejected subcutaneous flank tumors (a non-privileged site). However, the vaccine failed to protect mice from even a small number of tumor cells transplanted into the immune-privileged anterior chamber. Surprisingly, immunized mice that were simultaneously challenged with subcutaneous and anterior chamber tumors were unable to eliminate tumors at either site. The failure of systemic protective immunity coincided with the loss of tumor-specific delayed hypersensitivity and cytotoxic T cells. We conclude that tumor cell vaccines that induce complete protection against tumors in non-immune-privileged sites fail to protect against the same tumor within an ocular immune-privileged site. Moreover, a tumor that escapes elimination within the eye can terminate systemic protective immunity that is induced by the tumor cell vaccine.
Chen
Peter W
PW
Department of Ophthalmology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9057, USA. Peter.Chen@utsouthwestern.edu
Ksander
Bruce R
BR
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D005134:Eye Neoplasms / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D034801:Mastocytoma / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D018664:Interleukin-12