Details

Autor(en) / Beteiligte

• Kimura, Yoshitaka
• Inoue, Asuka
• Hangai, Sho
• Saijo, Shinobu
• Negishi, Hideo
• Nishio, Junko
• Yamasaki, Sho
• Iwakura, Yoichiro
• Yanai, Hideyuki
• Taniguchi, Tadatsugu

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-12, Vol.113 (49), p.14097-14102

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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, tomediate 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.