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

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

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 BennerChristina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, Dirk Jaeger

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Résumé

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.

langue originale	Anglais
Pages (de - à)	587-601
Nombre de pages	15
journal	Cancer Cell
Volume	29
Numéro de publication	4
Les DOIs	https://doi.org/10.1016/j.ccell.2016.03.005
état	Publié - 11 avr. 2016

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10.1016/j.ccell.2016.03.005

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Halama, N., Zoernig, I., Berthel, A., Kahlert, C., Klupp, F., Suarez-Carmona, M., Suetterlin, T., Brand, K., Krauss, J., Lasitschka, F., Lerchl, T., Luckner-Minden, C., Ulrich, A., Koch, M., Weitz, J., Schneider, M., Buechler, M. W., Zitvogel, L., Herrmann, T., ... Jaeger, D. (2016). Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients. Cancer Cell, 29(4), 587-601. https://doi.org/10.1016/j.ccell.2016.03.005

@article{d0c13219e3b84d26acd6871ed68c55b9,

title = "Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients",

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.",

author = "Niels Halama and Inka Zoernig and Anna Berthel and Christoph Kahlert and Fee Klupp and Meggy Suarez-Carmona and Thomas Suetterlin and Karsten Brand and Juergen Krauss and Felix Lasitschka and Tina Lerchl and Claudia Luckner-Minden and Alexis Ulrich and Moritz Koch and Juergen Weitz and Martin Schneider and Buechler, {Markus W.} and Laurence Zitvogel and Thomas Herrmann and Axel Benner and Christina Kunz and Stephan Luecke and Christoph Springfeld and Niels Grabe and Falk, {Christine S.} and Dirk Jaeger",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = apr,

day = "11",

doi = "10.1016/j.ccell.2016.03.005",

language = "English",

volume = "29",

pages = "587--601",

journal = "Cancer Cell",

issn = "1535-6108",

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Halama, N, Zoernig, I, Berthel, A, Kahlert, C, Klupp, F, Suarez-Carmona, M, Suetterlin, T, Brand, K, Krauss, J, Lasitschka, F, Lerchl, T, Luckner-Minden, C, Ulrich, A, Koch, M, Weitz, J, Schneider, M, Buechler, MW, Zitvogel, L, Herrmann, T, Benner, A, Kunz, C, Luecke, S, Springfeld, C, Grabe, N, Falk, CS & Jaeger, D 2016, 'Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients', Cancer Cell, VOL. 29, Numéro 4, p. 587-601. https://doi.org/10.1016/j.ccell.2016.03.005

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T1 - Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients

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 - Luecke, Stephan

AU - Springfeld, Christoph

AU - Grabe, Niels

AU - Falk, Christine S.

AU - Jaeger, Dirk

PY - 2016/4/11

Y1 - 2016/4/11

N2 - 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.

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.

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SN - 1535-6108

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SP - 587

EP - 601

JO - Cancer Cell

JF - Cancer Cell

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