Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is mediated by NK cells. (3rd April 2018)

• Record Type: Journal Article
• Authors: Foerster, Friedrich; Boegel, Sebastian; Heck, Rosario; Pickert, Geetha; Rüssel, Nina; Rosigkeit, Sebastian; Bros, Matthias; Strobl, Stephanie; Kaps, Leonard; Aslam, Misbah; Diken, Mustafa; Castle, John; Sahin, Ugur; Tuettenberg, Andrea; Bockamp, Ernesto; Schuppan, Detlef
• Is Part Of: Oncoimmunology. Volume 7:Number 4(2018)
• Publication Date: 2018-04-03
• Subjects: metastasis -- innate immunity -- cancer immunology -- liver -- macrophages -- NK cells; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1409929
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: The B16F10 murine melanoma cell line displays a low expression of MHC class I molecules favoring immune evasion and metastases in immunocompetent C57 BL/6 wild-type mice. Here, we generated metastases to the liver, an organ that is skewed towards immune tolerance, by intrasplenic injection of B16F10 cells in syngeneic C57 BL/6 compared to allogeneic Balb/c mice. Surprisingly, Balb/c mice, which usually display a pronounced M2 macrophage and Th2 T cell polarization, were ∼3 times more susceptible to metastasis than C57 BL/6 mice, despite a much higher M1 and Th1 T cell immune response. The anti-metastatic advantage of C57 BL/6 mice could be attributed to a more potent NK-cell mediated cytotoxicity against B16F10 cells. Our findings highlight the role of NK cells in innate anti-tumor immunity in the context of the liver – particularly against highly aggressive MHC I-deficient cancer cells. Moreover, the B16F10 model of melanoma liver metastasis is suited for developing novel therapies targeting innate NK cell related immunity in liver metastases and liver cancer.