title: Angiostatic effects of NK cell-derived IFN-γ counteracted by tumour cell Bcl-xL expression.
abstract: Anti-apoptotic proteins that block death receptor-mediated apoptosis favour tumour evasion of the immune system, leading to enhanced tumour progression. However, it is unclear whether blocking the mitochondrial pathway of apoptosis will protect tumours from immune cell attack. Here, we report that the anti-apoptotic protein Bcl-xL , known for its ability to block the mitochondrial pathway of apoptosis, exerted tumour-progressive activity in a murine lymphoma model. Bcl-xL overexpressing tumours exhibited a more aggressive development than control tumours. Surprisingly, Bcl-xL protection of tumours from NK cell-mediated attack did not involve protection from NK cell-mediated cytotoxicity. Instead, Bcl-xL -blocked apoptosis resulting from hypoxia and/or nutrient loss associated with the inhibition of angiogenesis caused by NK cell-secreted IFN-γ. These results support the notion that NK cells may inhibit tumour growth also by mechanisms other than direct cytotoxicity. Hence, the present results unravel a pathway by which tumours with a block in the mitochondrial pathway of apoptosis can evade the immune system.
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Microbiology Tumor- and Cell- Biology, Karolinska Institutet, Stockholm, Sweden; Indonesia International Institute for Life-Sciences, Jakarta Timur, Jakarta, Indonesia.
authors: R P A
authors: RP
authors: Wallin
authors: V S
authors: VS
authors: Sundquist
authors: E
authors: E
authors: Bråkenhielm
authors: Y
authors: Y
authors: Cao
authors: H-G
authors: HG
authors: Ljunggren
authors: A
authors: A
authors: Grandien
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003510:Cyclohexanes / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology; D019139:Tumor Escape; D051020:bcl-X Protein / Q000502:physiology*
chemical_list: D003510:Cyclohexanes; D012717:Sesquiterpenes; D051020:bcl-X Protein; D007371:Interferon-gamma; D000077609:O-(Chloroacetylcarbamoyl)fumagillol