Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment

被引：159

作者：

Kfoury, Youmna ^{[1
,2
,3
]}

Baryawno, Ninib ^{[1
,2
,3
,4
]}

Severe, Nicolas ^{[1
,2
,3
]}

Mei, Shenglin ^{[5
]}

Gustafsson, Karin ^{[1
,2
,3
]}

Hirz, Taghreed ^{[1
,2
,3
]}

Brouse, Thomas ^{[1
]}

Scadden, Elizabeth W. ^{[1
]}

Igolkina, Anna A. ^{[6
]}

Kokkaliaris, Konstantinos ^{[1
,2
,3
]}

Choi, Bryan D. ^{[7
]}

Barkas, Nikolas ^{[5
]}

Randolph, Mark A. ^{[8
]}

Shin, John H. ^{[7
]}

Saylor, Philip J. ^{[9
]}

Scadden, David T. ^{[1
,2
,3
]}

Sykes, David B. ^{[1
,2
,3
]}

Kharchenko, Peter, V ^{[2
,5
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[2] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[4] Karolinska Inst, Dept Womens Hlth & Childrens, Childhood Canc Res Unit, Stockholm, Sweden

[5] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA

[6] St Petersburg Polytech Univ, St Petersburg, Russia

[7] Harvard Med Sch, Dept Neurosurg, Boston, MA 02115 USA

[8] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA

[9] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA

来源：

CANCER CELL | 2021年 / 39卷 / 11期

基金：

瑞典研究理事会;

关键词：

REGULATORY T-CELLS; RNA-SEQ; CCL20; MITOXANTRONE; PREDNISONE; EXPRESSION; DOCETAXEL; SURVIVAL; POLARIZATION; RECRUITMENT;

D O I：

10.1016/j.ccell.2021.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Bone metastases are devastating complications of cancer. They are particularly common in prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy. We seek to define distinct features of the bone marrow (BM) microenvironment by analyzing single cells from bone metastatic prostate tumors, involved BM, uninvolved BM, and BM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCa is associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to PCa bone metastases. The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCa bone metastases restores T cell reactivity and significantly prolongs animal survival. Comparative high-resolution analysis of PCa bone metastases shows a targeted approach for relieving local immunosuppression for therapeutic effect.

引用

页码：1464 / +

页数：24

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