[PDF][PDF] Tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients
N Halama, I Zoernig, A Berthel, C Kahlert, F Klupp… - Cancer cell, 2016 - cell.com
N Halama, I Zoernig, A Berthel, C Kahlert, F Klupp, M Suarez-Carmona, T Suetterlin…
Cancer cell, 2016•cell.comThe 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 …
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 …
Summary
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.
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