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Cancer Cell. 2016 Apr 11;29(4):587-601. doi: 10.1016/j.ccell.2016.03.005.

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

Author information

1
Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany; Institute for Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany. Electronic address: niels.halama@nct-heidelberg.de.
2
Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
3
Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany.
4
Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany; Department of Surgery, University Hospital Dresden, 01307 Dresden, Germany.
5
Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
6
Institute for Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
7
Department of Surgery, University Hospital Dresden, 01307 Dresden, Germany.
8
INSERM U1015, Institut Gustave Roussy (IGR), 94805 Villejuif, France.
9
Department of Internal Medicine I, Klinikum Idar-Oberstein, 55743 Idar Oberstein, Germany.
10
Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
11
Institute of Transplant Immunology, Integrated Research and Treatment Center Transplantation, Hannover Medical School, 30625 Hannover, Germany.

Abstract

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 patient-derived 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.

PMID:
27070705
DOI:
10.1016/j.ccell.2016.03.005
[Indexed for MEDLINE]
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