Spontaneous mammary carcinomas fail to induce an immune response in syngeneic FVBN202 neu transgenic mice.
FVBN202 mice, which are transgenic for the rat neu gene, spontaneously develop mammary carcinomas between 6 and 7 months of age. We investigated whether these spontaneous tumors (spontaneous breast carcinoma cells, SBCC) could elicit an immune response in naive 6- to 8-week-old FVBN202 transgenic and FVBN nontransgenic mice. After s.c. injection of SBCC, the recently activated T cells, which were identified by their reduced expression of CD62L (L-selectin), were isolated from the draining lymph nodes, expanded with anti-CD3 and IL-2, and their cytokine response to tumor cells in vitro was analyzed. Tumor-vaccine draining lymph node lymphocytes (TVDLN) from transgenic mice failed to make IFN-gamma in response to the tumor cells. However, TVDLN from the nontransgenic mice exhibited a tumor-specific IFN-gamma response against the SBCC. This indicates that the SBCC are immunogenic. The lack of response in transgenic mice could not be attributed to cytokine immune deviation or T-cell signaling defects. Although transgenic mice were tolerant to their own tumors, their immune competence was established by their ability to respond in an allogeneic mixed lymphocyte reaction, to reject an allogeneic breast carcinoma cell line, and to produce a tumor-specific IFN-gamma response against a syngeneic cancer cell line. This transgenic mouse model provides the opportunity to investigate the immune response against a primary tumor cell culture rather than cell lines or clones and should prove useful for developing immunotherapies that overcome tolerance to self-tumor antigens.
Laboratory of Cellular Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Oregon Cancer Center, Portland, Oregon, USA. RKurt@providence.org
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Kurt
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Whitaker
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A
Baher
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Seung
W J
WJ
Urba
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018734:Genes, erbB-2; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007519:Isoantigens; D019041:L-Selectin; D018719:Erb-b2 Receptor Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell