Rat adenocarcinoma 13762 expresses tumor rejection antigens but tumor-bearing animals exhibit tumor-specific immunosuppression.
Rat adenocarcinoma 13762 was adapted to continuous growth in culture and used in a variety of experiments to investigate the immune response to inoculation of animals with replication-defective tumor cells. The results demonstrate that 13762 cells express tumor-specific tumor rejection antigens that elicit protective immunity to tumorigenic challenge. By several criteria there is no apparent humoral component of the anti-tumor immunity; however, anti-tumor immunity is characterized by nylon-wool nonadherent spleen T cells. Anti-tumor T cells demonstrate tumoricidal activity in local adoptive transfer assays and are not found in spleens of naive animals or animals immunized against either nontumorigenic Rat 1 cells or a syngeneic fibrosarcoma. Despite the expression of tumor rejection antigens 13762 tumor, and the demonstrable ability of injection of irradiated tumor to induce anti-tumor immunity, tumors elicited in unimmunized syngeneic animals grow progressively. The reasons for growth of antigenic tumor are unknown but are shown not to be due to defective antigen expression in 13762 tumor since, in addition to being able to elicit T cell immune response in immunized animals, 13762 tumor expresses MHC Class I molecules and can be a target for allogeneic T cell recognition in vitro. These data suggest that in tumor-bearing animals an effective anti-tumor immune response is either not initiated or down-regulated. Since animals bearing 13762 tumors can be immunized against an unrelated syngeneic sarcoma, can produce humoral responses to several protein antigens, and can produce delayed type hypersensitivity response against dinitrofluorobenzene, the immune response to 13762-induced tumors appears specifically suppressed. In support of this contention, 13762 cells express high levels of transforming growth factor beta 1 in vitro which is postulated to impact upon the nascent anti-tumor immune response.
Frey
A B
AB
Department of Cell Biology, New York University School of Medicine, New York 10016.
Appleman
L J
LJ
D000230:Adenocarcinoma / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D004139:Dinitrofluorobenzene / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005354:Fibrosarcoma / Q000276:immunology; D005434:Flow Cytometry; D006386:Hemagglutination Tests; D006433:Hemocyanins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D006433:Hemocyanins; D004139:Dinitrofluorobenzene; C032808:keyhole-limpet hemocyanin