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Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients.
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.
Afiliação
  • Halama N; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany; Institute for Immunology, University H
  • Zoernig I; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Berthel A; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany.
  • Kahlert C; Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany; Department of Surgery, University Hospital Dresden, 01307 Dresden, Germany.
  • Klupp F; Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Suarez-Carmona M; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Suetterlin T; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany.
  • Brand K; Institute for Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Krauss J; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Lasitschka F; Institute for Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Lerchl T; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany.
  • Luckner-Minden C; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Ulrich A; Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Koch M; Department of Surgery, University Hospital Dresden, 01307 Dresden, Germany.
  • Weitz J; Department of Surgery, University Hospital Dresden, 01307 Dresden, Germany.
  • Schneider M; Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Buechler MW; Department of Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Zitvogel L; INSERM U1015, Institut Gustave Roussy (IGR), 94805 Villejuif, France.
  • Herrmann T; Department of Internal Medicine I, Klinikum Idar-Oberstein, 55743 Idar Oberstein, Germany.
  • Benner A; Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Kunz C; Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Luecke S; Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Springfeld C; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Grabe N; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany.
  • Falk CS; Institute of Transplant Immunology, Integrated Research and Treatment Center Transplantation, Hannover Medical School, 30625 Hannover, Germany.
  • Jaeger D; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, 69120 Heidelberg, Germany.
Cancer Cell ; 29(4): 587-601, 2016 Apr 11.
Article em En | MEDLINE | ID: mdl-27070705
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenocarcinoma / Quimiocina CCL5 / Receptores CCR5 / Terapia de Alvo Molecular / Neoplasias Hepáticas / Proteínas de Neoplasias Idioma: En Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenocarcinoma / Quimiocina CCL5 / Receptores CCR5 / Terapia de Alvo Molecular / Neoplasias Hepáticas / Proteínas de Neoplasias Idioma: En Ano de publicação: 2016 Tipo de documento: Article