Murine B16 melanoma vaccination-induced tumor immunity: identification of specific immune cells and functions involved.
Vaccination using inactivated B16 melanoma cells that have been treated in vitro for > 2 weeks with interferon-alpha (IFN-alpha) (B16alpha cells) has been shown to elicit a protective host antitumor immunity. In these studies, vaccination with B16alpha cells has been shown to provide protection against primary B16 tumor challenge, established B16 tumors, and metastatic B16 tumors. Specific immune cells and factors that might mediate this tumor immunity have now been evaluated. Macrophage depletion studies suggest that macrophage function is required for expression of tumor immunity either for processing of antigen or for cytokine production but that macrophage function is not involved in direct cytotoxicity against the B16 challenge tumor. CD8(+) T cell depletion studies show that cytotoxic T cell function is required for expression of tumor immunity. Syngeneic knockout mouse experiments offer further insights into the immune cells and factors that mediate the development and expression of tumor immunity. First, interleukin-12 (IL-12) knockout mouse experiments identify IL-12 as an important cytokine in mediating the development of tumor immunity. Second, specific knockout mouse experiments show that tumor immunity requires the function of CD4(+) T cells, CD8(+) T cells, and natural killer (NK) cells. Third, specific knockout mouse experiments show that tumor immunity does not require the function of B cells. The results suggest that vaccination with inactivated B16alpha cells induces an active, cell-mediated immunity to B16 melanoma cells. The tumor vaccination protocol with B16alpha cell vaccinations establishes a potent tumor immunity against B16 melanoma tumors in mice and may serve as a model for induction of tumor immunity against primary or secondary melanoma tumors in humans.
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Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Fleischmann
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D018664:Interleukin-12 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; D018664:Interleukin-12