CSF1 Receptor Targeting in Prostate Cancer Reverses Macrophage-Mediated Resistance to Androgen Blockade Therapy

Jemima Escamilla(University of California, Los Angeles), Shiruyeh Schokrpur(University of California, Los Angeles), Connie Liu(University of California, Los Angeles), Saul J. Priceman(City Of Hope National Medical Center), Diana Moughon(University of California, Los Angeles), Ziyue Karen Jiang(University of California, Los Angeles), Frédéric Pouliot(Centre hospitalier universitaire de Québec), Clara E. Magyar(University of California, Los Angeles), James L. Sung(University of California, Los Angeles), Jingying Xu(University of California, Los Angeles), Gang Deng(University of California, Los Angeles), Brian L. West(Molecular Pathology Laboratory Network (United States)), Gideon Bollag(Molecular Pathology Laboratory Network (United States)), Yves Fradet(Centre hospitalier universitaire de Québec), Louis Lacombe(Centre hospitalier universitaire de Québec), Michael E. Jung(University of California, Los Angeles), Jiaoti Huang(University of California, Los Angeles), Lily Wu(University of California, Los Angeles)
Cancer Research
March 3, 2015
10.1158/0008-5472.can-14-0992
Cited by 214Open Access
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Abstract

Growing evidence suggests that tumor-associated macrophages (TAM) promote cancer progression and therapeutic resistance by enhancing angiogenesis, matrix-remodeling, and immunosuppression. In this study, prostate cancer under androgen blockade therapy (ABT) was investigated, demonstrating that TAMs contribute to prostate cancer disease recurrence through paracrine signaling processes. ABT induced the tumor cells to express macrophage colony-stimulating factor 1 (M-CSF1 or CSF1) and other cytokines that recruit and modulate macrophages, causing a significant increase in TAM infiltration. Inhibitors of CSF1 signaling through its receptor, CSF1R, were tested in combination with ABT, demonstrating that blockade of TAM influx in this setting disrupts tumor promotion and sustains a more durable therapeutic response compared with ABT alone.

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