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

被引：173

作者：

Escamilla, Jemima ^{[1
]}

Schokrpur, Shiruyeh ^{[1
]}

Liu, Connie ^{[1
]}

Priceman, Saul J. ^{[2
]}

Moughon, Diana ^{[1
]}

Jiang, Ziyue ^{[1
,3
]}

Pouliot, Frederic ^{[4
]}

Magyar, Clara ^{[5
]}

Sung, James L. ^{[1
]}

Xu, Jingying ^{[1
]}

Deng, Gang ^{[6
]}

West, Brian L. ^{[7
]}

Bollag, Gideon ^{[7
]}

Fradet, Yves ^{[4
]}

Lacombe, Louis ^{[4
]}

Jung, Michael E. ^{[6
]}

Huang, Jiaoti ^{[5
]}

Wu, Lily ^{[1
,3
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[2] Beckman Res Inst City Hope, Dept Canc Immunotherapeut & Tumor Immunol, Duarte, CA USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA

[4] CHU Quebec, Div Urol, Dept Surg, Quebec City, PQ, Canada

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA

[7] Plexxikon Inc, Berkeley, CA USA

来源：

CANCER RESEARCH | 2015年 / 75卷 / 06期

关键词：

TUMOR-ASSOCIATED MACROPHAGES; STIMULATING FACTOR-1 RECEPTOR; INFILTRATING MYELOID CELLS; TYROSINE KINASE INHIBITOR; IN-VIVO; CASTRATION; PROGRESSION; METASTASIS; INFLAMMATION; MECHANISMS;

D O I：

10.1158/0008-5472.CAN-14-0992

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C)2015 AACR.

引用

页码：950 / 962

页数：13

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