@article{oai:repo.qst.go.jp:00079070,
 author = {Terashima, Yuya and Toda, Etsuko and Itakura, Meiji and Otsuji, Mikiya and H.W. Shand, Francis and Okumura, Kazuhiro and Yoshinaga, Sosuke and Komohara, Yoshihiro and Takeda, Mitsuhiro and Kokubo, Kana and Meing-Chen, Chen and Yokoi, Sana and Rokutan, Hirofumi and Kofuku, Yutaka and Ohnishi, Koji and Ohira, Miki and Iizasa, Toshihiko and Nakano, Hirofumi and Okabe, Takayoshi and Kojima, Hirotatsu and Shimizu, Akira and Kanegasaki, Shiro and Ming-Rong, Zhang and Shimada, Ichio and Nagase, Hiroki and Terasawa, Hiroaki and Mastushima, Kouji and Zhang, Ming-Rong},
 journal = {Nature Communications},
 month = {Feb},
 note = {Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-deficiency markedly reduces tumor progression and decreases macrophage tumor-promoting activity. FROUNT is highly expressed in macrophages, and its myeloid-specific deletion impairs tumor growth. Further, the anti-alcoholism drug disulfiram (DSF) acts as a potent inhibitor of FROUNT. DSF interferes with FROUNT-chemokine receptor interactions via direct binding to a specific site of the chemokine receptor-binding domain of FROUNT, leading to inhibition of macrophage responses. DSF monotherapy reduces tumor progression and decreases macrophage tumor-promoting activity, as seen in the case of Frount-deficiency. Moreover, co-treatment with DSF and an immune checkpoint antibody synergistically inhibits tumor growth. Thus, inhibition of FROUNT by DSF represents a promising strategy for macrophage-targeted cancer therapy.},
 title = {Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties},
 volume = {11},
 year = {2020}
}