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

共 52 条

[21]

Halama N, 2010, ANAL QUANT CYTOL, V32, P333

[22] Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines [J].

Halama, Niels ;

Braun, Monika ;

Kahlert, Christoph ;

Spille, Anna ;

Quack, Christian ;

Rahbari, Nuh ;

Koch, Moritz ;

Weitz, Juergen ;

Kloor, Matthias ;

Zoernig, Inka ;

Schirmacher, Peter ;

Brand, Karsten ;

Grabe, Niels ;

Falk, Christine S. .

CLINICAL CANCER RESEARCH, 2011, 17 (04) :678-689

[23] Estimation of Immune Cell Densities in Immune Cell Conglomerates: An Approach for High-Throughput Quantification [J].

Halama, Niels ;

Zoernig, Inka ;

Spille, Anna ;

Westphal, Kathi ;

Schirmacher, Peter ;

Jaeger, Dirk ;

Grabe, Niels .

PLOS ONE, 2009, 4 (11)

[24]

Halama Niels, 2009, Cancer Immun, V9, P1

[25] Assessing oncologic benefit in clinical trials of immunotherapy agents [J].

Hales, R. K. ;

Banchereau, J. ;

Ribas, A. ;

Tarhini, A. A. ;

Weber, J. S. ;

Fox, B. A. ;

Drake, C. G. .

ANNALS OF ONCOLOGY, 2010, 21 (10) :1944-1951

[26] Direct Effects of Type I Interferons on Cells of the Immune System [J].

Hervas-Stubbs, Sandra ;

Luis Perez-Gracia, Jose ;

Rouzaut, Ana ;

Sanmamed, Miguel F. ;

Le Bon, Agnes ;

Melero, Ignacio .

CLINICAL CANCER RESEARCH, 2011, 17 (09) :2619-2627

[27] SNAIL Regulates Interleukin-8 Expression, Stem Cell-Like Activity, and Tumorigenicity of Human Colorectal Carcinoma Cells [J].

Hwang, Wei-Lun ;

Yang, Muh-Hwa ;

Tsai, Ming-Long ;

Lan, Hsin-Yi ;

Su, Shu-Han ;

Chang, Shih-Ching ;

Teng, Hao-Wei ;

Yang, Shung-Haur ;

Lan, Yuan-Tzu ;

Chiou, Shih-Hwa ;

Wang, Hsei-Wei .

GASTROENTEROLOGY, 2011, 141 (01) :279-U382

[28] Sequential metastases of colorectal cancer Immunophenotypes and spatial distributions of infiltrating immune cells in relation to time and treatments [J].

Keim, Sophia ;

Zoernig, Inka ;

Spille, Anna ;

Lahrmann, Bernd ;

Brand, Karsten ;

Herpel, Esther ;

Grabe, Niels ;

Jaeger, Dirk ;

Halama, Niels .

ONCOIMMUNOLOGY, 2012, 1 (05) :593-599

[29] Parallel progression of primary tumours and metastases [J].

Klein, Christoph A. .

NATURE REVIEWS CANCER, 2009, 9 (04) :302-312

[30] Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1 [J].

Kuang, Dong-Ming ;

Zhao, Qiyi ;

Peng, Chen ;

Xu, Jing ;

Zhang, Jing-Ping ;

Wu, Changyou ;

Zheng, Limin .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (06) :1327-1337

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