Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients

被引：419

作者：

Halama, Niels ^{[1
,2
,3
]}

Zoernig, Inka ^{[1
]}

Berthel, Anna ^{[1
,2
]}

Kahlert, Christoph ^{[4
]}

Klupp, Fee ^{[4
]}

Suarez-Carmona, Meggy ^{[1
]}

Suetterlin, Thomas ^{[1
,2
]}

Brand, Karsten ^{[5
]}

Krauss, Juergen ^{[1
]}

Lasitschka, Felix ^{[5
]}

Lerchl, Tina ^{[1
,2
]}

Luckner-Minden, Claudia ^{[1
]}

Ulrich, Alexis ^{[4
]}

Koch, Moritz ^{[6
]}

Weitz, Juergen ^{[6
]}

Schneider, Martin ^{[4
]}

Buechler, Markus W. ^{[4
]}

Zitvogel, Laurence ^{[7
]}

Herrmann, Thomas ^{[8
]}

Benner, Axel ^{[9
]}

Kunz, Christina ^{[9
]}

Luecke, Stephan ^{[9
]}

Springfeld, Christoph ^{[1
]}

Grabe, Niels ^{[1
,2
]}

Falk, Christine S. ^{[10
]}

Jaeger, Dirk ^{[1
,2
]}

机构：

[1] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Dept Med Oncol, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, BIOQUANT, Natl Ctr Tumor Dis, Tissue Imaging & Anal Ctr, D-69120 Heidelberg, Germany

[3] Univ Heidelberg Hosp, Inst Immunol, D-69120 Heidelberg, Germany

[4] Univ Heidelberg Hosp, Dept Surg, D-69120 Heidelberg, Germany

[5] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany

[6] Univ Hosp Dresden, Dept Surg, D-01307 Dresden, Germany

[7] IGR, INSERM U1015, F-94805 Villejuif, France

[8] Klinikum Idar Oberstein, Dept Internal Med 1, D-55743 Idar Oberstein, Germany

[9] German Canc Res Ctr, Div Biostat, D-69120 Heidelberg, Germany

[10] Hannover Med Sch, Integrated Res & Treatment Ctr Transplantat, Inst Transplant Immunol, D-30625 Hannover, Germany

来源：

CANCER CELL | 2016年 / 29卷 / 04期

关键词：

MIGRATION INHIBITORY FACTOR; CHEMOKINE RECEPTOR CCR5; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; IMMUNOTHERAPY; INFLAMMATION; CHEMOTHERAPY; PROGRESSION; ANTAGONIST; EXPRESSION;

D O I：

10.1016/j.ccell.2016.03.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The immune response influences the clinical course of colorectal cancer (CRC). Analyzing the invasive margin of human CRC liver metastases, we identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. CCR5 blockade in patientderived functional in vitro organotypic culture models showed a macrophage repolarization with anti-tumoral effects. These anti-tumoral effects were then confirmed in a phase I trial with a CCR5 antagonist in patients with liver metastases of advanced refractory CRC. Mitigation of tumor-promoting inflammation within the tumor tissue and objective tumor responses in CRC were observed.

引用

页码：587 / 601

页数：15

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