For men with castration-resistant prostate cancer (CRPC), androgen-deprivation therapy (ADT) often becomes ineffective requiring the addition of docetaxel, a proven effective chemotherapy option. Tumor-associated macrophages (TAMs) are known to provide protumorigenic influences that contribute to treatment failure. In this study, we examined the contribution of TAMs to docetaxel treatment. An increased infiltration of macrophages in CRPC tumors was observed after treatment with docetaxel. Prostate cancer cells treated with docetaxel released more macrophage colony-stimulating factor (M-CSF-1 or CSF-1), IL-10 and other factors, which can recruit and modulate circulating monocytes to promote their protumorigenic functions. Inhibition of CSF-1 receptor kinase signaling with a small molecule antagonist (PLX3397) in CRPC models significantly reduces the infiltration of TAMs and their influences. As such, the addition of PLX3397 to docetaxel treatment resulted in a more durable tumor growth suppression than docetaxel alone. This study reveals a rational strategy to abrogate the influences of TAMs and extend the treatment response to docetaxel in CRPC.
Author Info: (1) Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (2) Department of Urology 
Author Info: (1) Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (2) Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Department of Paediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA. (3) Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China. (4) Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China. (5) Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China. (6) Plexxikon Inc., Berkeley, California, USA. (7) Plexxikon Inc., Berkeley, California, USA. (8) Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (9) Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA. Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA. Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA. Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA. 
