Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona, Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W Buechler, Laurence Zitvogel, Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S Falk, Dirk Jaeger, Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona, Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W Buechler, Laurence Zitvogel, Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S Falk, Dirk Jaeger
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.
Copyright © 2016 Elsevier Inc. All rights reserved.
Source: PubMed