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Halama, Niels; Zoernig, Inka; Berthel, Anna; Kahlert, Christoph; Klupp, Fee; Suarez-Carmona, Meggy; Brand, Karsten; Krauss, Juergen; Lasitschka, Felix; Ulrich, Alexis; Weitz, Juergen; Schneider, Martin; Buechler, Markus; Zitvogel, Laurence; Herrmann, Thomas; Benner, Axel; Kunz, Christina; Luecke, Stephan; Springfeld, Christoph; Falk, Christine S.; Jaeger, Dirk

Abstract 3021: CCR5 inhibition: macrophage repolarization therapy for colorectal cancer

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  • Medientyp: E-Artikel
  • Titel: Abstract 3021: CCR5 inhibition: macrophage repolarization therapy for colorectal cancer
  • Beteiligte: Halama, Niels; Zoernig, Inka; Berthel, Anna; Kahlert, Christoph; Klupp, Fee; Suarez-Carmona, Meggy; Brand, Karsten; Krauss, Juergen; Lasitschka, Felix; Ulrich, Alexis; Weitz, Juergen; Schneider, Martin; Buechler, Markus; Zitvogel, Laurence; Herrmann, Thomas; Benner, Axel; Kunz, Christina; Luecke, Stephan; Springfeld, Christoph; Falk, Christine S.; Jaeger, Dirk
  • Erschienen: American Association for Cancer Research (AACR), 2017
  • Erschienen in: Cancer Research
  • Sprache: Englisch
  • DOI: 10.1158/1538-7445.am2017-3021
  • ISSN: 0008-5472; 1538-7445
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>In patients with metastatic colorectal cancer (CRC), the local immune response influences the clinical course. An in-depth analysis of the invasive margin of human CRC liver metastases revealed a distinct immunological microenvironment. Within this microenvironment, 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, creating an exploitive loop. CCR5 was found on macrophages, lymphocytes and on the vast majority of tumor cells. Inhibition of CCR5 in patient-derived functional in vitro organotypic culture models showed a promising macrophage repolarization with anti-tumoral effects. These effects are mediated by activation of an antiviral program in macrophages, leading to interferon and reactive oxygen species production and subsequent selective tumor cell death. These anti-tumoral effects were confirmed in a phase I trial with a CCR5 antagonist in 14 patients with liver metastases of advanced refractory CRC. Treatment with the oral CCR5 Inhibitor was very well tolerated and objective responses were seen, especially in combination with previously ineffective chemotherapy. Biopsies revealed mitigation of tumor-promoting inflammation within the tumor tissue, confirming the validity of the explant model and highlighting the feasbility of this approach. It furthermore shows the proof-of-concept for macrophage repolarization in cancer patients.</jats:p> <jats:p>Citation Format: Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona, Karsten Brand, Juergen Krauss, Felix Lasitschka, Alexis Ulrich, Juergen Weitz, Martin Schneider, Markus Buechler, Laurence Zitvogel, Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Christine S. Falk, Dirk Jaeger. CCR5 inhibition: macrophage repolarization therapy for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3021. doi:10.1158/1538-7445.AM2017-3021</jats:p>
  • Zugangsstatus: Freier Zugang