The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis.

Abstract

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.

• Authors: Yoshitaka Kimura, Asuka Inoue, Sho Hangai, Shinobu Saijo, Hideo Negishi, Junko Nishio, Sho Yamasaki, Yoichiro Iwakura, Hideyuki Yanai, Tadatsugu Taniguchi
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 49 Pg. 14097-14102 (12 06 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 27872290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Clec4d protein, mouse
• Lectins, C-Type
• Receptors, Immunologic
• dectin-2, mouse

Topics

• Animals
• Cell Line, Tumor
• Humans
• Kupffer Cells (physiology)
• Lectins, C-Type (genetics, metabolism)
• Liver Neoplasms, Experimental (secondary)
• Mice, Inbred C57BL
• Neoplasm Metastasis (immunology)
• Phagocytosis
• Receptors, Immunologic (metabolism)