Immunoprevention of mammary carcinoma in HER-2/neu transgenic mice is IFN-gamma and B cell dependent

• Published in: The Journal of immunology (1950) 2004-08, Vol.173 (4), p.2288-2296
• Main Authors: Nanni, Patrizia, Landuzzi, Lorena, Nicoletti, Giordano, De Giovanni, Carla, Rossi, Ilaria, Croci, Stefania, Astolfi, Annalisa, Iezzi, Manuela, Di Carlo, Emma, Musiani, Piero, Forni, Guido, Lollini, Pier-Luigi
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - immunology; Cancer Vaccines - immunology; Female; Immunohistochemistry; Interferon-gamma - deficiency; Interferon-gamma - genetics; Interferon-gamma - immunology; Mammary Neoplasms, Experimental - prevention & control; Mice; Mice, Transgenic; Receptor, ErbB-2 - deficiency; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.4.2288

A vaccine combining IL-12 and allogeneic mammary carcinoma cells expressing p185(neu) completely prevents tumor onset in HER-2/neu transgenic BALB/c mice (NeuT mice). The immune protection elicited was independent from CTL activity. We now formally prove that tumor prevention is mainly based on the production of anti-p185(neu) Abs. In the present studies, NeuT mice were crossed with knockout mice lacking IFN-gamma production (IFN-gamma(-/-)) or with B cell-deficient mice (microMT). Vaccination did not protect NeuT-IFN-gamma(-/-) mice, thus confirming a central role of IFN-gamma. The block of Ab production in NeuT-microMT mice was incomplete. About one third of NeuT-microMT mice failed to produce Abs and displayed a rapid tumor onset. By contrast, those NeuT-microMT mice that responded to the vaccine with a robust production of anti-p185(neu) Ab displayed a markedly delayed tumor onset. In these NeuT-microMT mice, the vaccine induced a lower level of IgG2a and IgG3 and a higher level of IgG2b than in NeuT mice. Moreover, NeuT-microMT mice failed to produce anti-MHC class I Abs in response to allogeneic H-2(q) molecules present in the cell vaccine. These findings show that inhibition of HER-2/neu carcinogenesis depends on cytokines and specific Abs, and that a highly effective vaccine can rescue Ab production even in B cell-deficient mice.