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Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-γ production by tumor-associated macrophages


To whom correspondence should be addressed. E-mail: takeya@kumamoto-u.ac.jp


Class A scavenger receptors (SR-A, CD204) are highly expressed in tumor-associated macrophages (TAM). To investigate the function of SR-A in TAM, wild-type and SR-A-deficient (SR-A−/−) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR-A−/− mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)-γ mRNA increased significantly in tumor tissues from SR-A−/− mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN-γ production by cultured macrophages, and production of NO and IFN-γ increased in SR-A−/− macrophages in vitro. IFN-β production by cultured macrophages was also elevated in SR-A−/− macrophages in vitro. These results suggested that the antitumor activity of macrophages increased in SR-A−/− mice because of upregulation of NO and IFN-γ production. These data indicate an important role of SR-A in regulating TAM function by inhibiting toll-like receptor (TLR)4–IFN-β signaling. (Cancer Sci 2009); 00: 000–000)