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Enhanced in vivo sensitivity of in vitro interferon-treated B16 melanoma cells to CD8 cells and activated macrophages.
- Source :
-
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research [J Interferon Cytokine Res] 1996 Oct; Vol. 16 (10), pp. 805-12. - Publication Year :
- 1996
-
Abstract
- Mouse B16 melanoma cells maintained in vitro in the presence of interferon (IFN)-alpha become resistant to the in vitro antiproliferative effects of IFN-alpha. However, IFN-alpha-treated mice inoculated with these in vitro IFN-treated cells (B16 alpha res cells) have significantly increased life spans (ILS) and significantly higher cure rates than IFN-alpha-treated mice inoculated with B16 cells. This unexpectedly greater sensitivity of B16 alpha res cells to the in vivo antitumor effects of IFN-alpha was evaluated by in vivo cell depletion experiments. Depletion of either activated peritoneal macrophages or cytotoxic T lymphocytes (CTL) reduced the ILS of IFN-treated B16 alpha res-inoculated mice to a level comparable to that of IFN-treated B16-inoculated mice. Depletion of natural killer (NK) cells did not affect the ILS for IFN-treated B16 alpha res-inoculated mice. These studies indicate that activated macrophage and CD8 cell function, but not NK cell function, is important for the enhanced antitumor effects induced by IFN-alpha against B16 alpha res cells. Macrophage killing was unlikely to be mediated by TNF-alpha or IL-1 as B16 and B16 alpha res cells were equally sensitive to TNF-alpha and insensitive to IL-1 in vitro. Further, H-2K antigen expression is significantly more readily inducible on B16 alpha res cells than on B16 cells, consistent with enhanced CD8-mediated killing due to increased MHC class I antigen expression.
- Subjects :
- Analysis of Variance
Animals
Antigens, Neoplasm drug effects
Evaluation Studies as Topic
Female
H-2 Antigens drug effects
Killer Cells, Natural immunology
Melanoma, Experimental immunology
Mice
Mice, Inbred C57BL
Recombinant Proteins
Survival Rate
Tumor Cells, Cultured
Antineoplastic Agents therapeutic use
CD8-Positive T-Lymphocytes immunology
Interferon Type I therapeutic use
Macrophage Activation immunology
Macrophages, Peritoneal immunology
Melanoma, Experimental drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1079-9907
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
- Publication Type :
- Academic Journal
- Accession number :
- 8910765
- Full Text :
- https://doi.org/10.1089/jir.1996.16.805