Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
2016-04-11 | journal article; research paper
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Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Halama, N.; Zoernig, I.; Berthel, A.; Kahlert, C.; Klupp, F.; Suarez-Carmona, M. & Suetterlin, T. et al. (2016)
Cancer Cell, 29(4) pp. 587-601. DOI: https://doi.org/10.1016/j.ccell.2016.03.005
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Details
- Authors
- Halama, Niels; Zoernig, Inka; Berthel, Anna; Kahlert, Christoph; Klupp, Fee; Suarez-Carmona, Meggy; Suetterlin, Thomas; Brand, Karsten; Krauss, Juergen; Lasitschka, Felix; Lerchl, Tina; Luckner-Minden, Claudia; Ulrich, Alexis; Koch, Moritz; Weitz, Juergen; Schneider, Martin; Buechler, Markus W.; Zitvogel, Laurence; Herrmann, Thomas; Benner, Axel; Kunz, Christina; Luecke, Stephan; Springfeld, Christoph; Grabe, Niels ; Falk, Christine S.; Jaeger, Dirk
- 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.
- Issue Date
- 11-April-2016
- Journal
- Cancer Cell
- ISSN
- 1535-6108
- eISSN
- 1878-3686
- Language
- English