期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：49
页码：14097-14102
DOI：10.1073/pnas.1617903113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe liver is a common site for metastatic disease, and liver metastasis is strongly correlated with poor prognosis. Therefore, an understanding of how liver metastasis is regulated by the immune system is one of the most important issues in cancer immunology. Liver-resident immune cells may either suppress or promote liver metastasis. In this study, we show that Dectin-2 and macrophage C-type lectin, both of which belong to the C-type lectin family of innate receptors, is expressed on resident liver macrophages known as Kupffer cells and play critical roles in the suppression of liver metastasis by enhancing the cells phagocytotic activity against cancer cells. Our study sheds light on the protective role of Kupffer cells in liver metastasis with therapeutic implications. Tumor metastasis is the cause of most cancer deaths. Although metastases can form in multiple end organs, the liver is recognized as a highly permissive organ. Nevertheless, there is evidence for immune cell-mediated mechanisms that function to suppress liver metastasis by certain tumors, although the underlying mechanisms for the suppression of metastasis remain elusive. Here, we show that Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical for the suppression of liver metastasis of cancer cells. We provide evidence that Dectin-2 functions in resident macrophages in the liver, known as Kupffer cells, to mediate the uptake and clearance of cancer cells. Interestingly, Kupffer cells are selectively endowed with Dectin-2-dependent phagocytotic activity, with neither bone marrow-derived macrophages nor alveolar macrophages showing this potential. Concordantly, subcutaneous primary tumor growth and lung metastasis are not affected by the absence of Dectin-2. In addition, macrophage C-type lectin, a CLR known to be complex with Dectin-2, also contributes to the suppression of liver metastasis. Collectively, these results highlight the hitherto poorly understood mechanism of Kupffer cell-mediated control of metastasis that is mediated by the CLR innate receptor family, with implications for the development of anticancer therapy targeting CLRs.
