TY - JOUR
AU - Halama, Niels
AU - Zoernig, Inka
AU - Berthel, Anna
AU - Kahlert, Christoph
AU - Klupp, Fee
AU - Suarez-Carmona, Meggy
AU - Suetterlin, Thomas
AU - Brand, Karsten
AU - Krauss, Juergen
AU - Lasitschka, Felix
AU - Lerchl, Tina
AU - Luckner-Minden, Claudia
AU - Ulrich, Alexis
AU - Koch, Moritz
AU - Weitz, Juergen
AU - Schneider, Martin
AU - Buechler, Markus W
AU - Zitvogel, Laurence
AU - Herrmann, Thomas
AU - Benner, Axel
AU - Kunz, Christina
AU - Lücke, Stephan
AU - Springfeld, Christoph
AU - Grabe, Niels
AU - Falk, Christine S
AU - Jäger, Dirk
TI - Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients.
JO - Cancer cell
VL - 29
IS - 4
SN - 1535-6108
CY - Cambridge, Mass.
PB - Cell Press
M1 - DKFZ-2017-02077
SP - 587 - 601
PY - 2016
AB - 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.
KW - CCL5 protein, human (NLM Chemicals)
KW - CCR5 protein, human (NLM Chemicals)
KW - Chemokine CCL5 (NLM Chemicals)
KW - Chemokines (NLM Chemicals)
KW - Cyclohexanes (NLM Chemicals)
KW - Interferon-alpha (NLM Chemicals)
KW - Neoplasm Proteins (NLM Chemicals)
KW - Phenylurea Compounds (NLM Chemicals)
KW - Pyridines (NLM Chemicals)
KW - Receptors, CCR5 (NLM Chemicals)
KW - STAT3 Transcription Factor (NLM Chemicals)
KW - STAT3 protein, human (NLM Chemicals)
KW - Triazoles (NLM Chemicals)
KW - Clodronic Acid (NLM Chemicals)
KW - regorafenib (NLM Chemicals)
KW - maraviroc (NLM Chemicals)
KW - NG-Nitroarginine Methyl Ester (NLM Chemicals)
LB - PUB:(DE-HGF)16
C6 - pmid:27070705
DO - DOI:10.1016/j.ccell.2016.03.005
UR - https://inrepo02.dkfz.de/record/125953
ER -