Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines
-
- Niels Halama
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Monika Braun
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Christoph Kahlert
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Anna Spille
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Christian Quack
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Nuh Rahbari
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Moritz Koch
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Jürgen Weitz
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Matthias Kloor
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Inka Zoernig
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Peter Schirmacher
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Karsten Brand
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Niels Grabe
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
-
- Christine S. Falk
- Authors' Affiliations: 1Medical Oncology, National Center for Tumor Diseases; and 2Immune Monitoring Unit G101, German Cancer Research Center (DKFZ), NCT National Center for Tumor Diseases and Institute for Immunology, University Heidelberg, Germany; 3Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; 4Department of Surgery; 5Institute of Pathology; and 6Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany; and 7Department of Transplantation Immunology, IFB-Tx, Hannover Medical School, MHH, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
抄録
<jats:title>Abstract</jats:title> <jats:p>Purpose: Tumor infiltrating T lymphocytes in colorectal cancer (CRC) have prognostic impact, but the role of natural killer (NK) cells in CRC tissue is unclear. The contribution of intratumoral cytokines and chemokines in shaping the composition of the inflammatory lymphocytic infiltrate is also unclear.</jats:p> <jats:p>Experimental Design: In this study, localization and densities of NK and T cells within primary CRC, CRC liver metastases, adenomas, and normal tissues were analyzed on whole tissue sections from 112 patients. In a subset of these patients, the most important 50 cytokines and chemokines were quantified in paired serum, primary CRC and adjacent mucosa samples and in CRC liver metastases and correlated with NK and T-cell infiltration, respectively.</jats:p> <jats:p>Results: The various compartments displayed characteristic differences like significantly higher chemokine concentrations in CRC tissue. Most importantly, despite high local chemokine levels, NK cells were generally scarce within CRC tumor tissues, independent of human leukocyte antigen (HLA) class I expression. Adjacent normal mucosa contained normal levels of NK cells. In contrast, corresponding T-cell numbers varied substantially and were positively correlated with higher chemokine levels.</jats:p> <jats:p>Conclusions: Our findings indicate a distinct regulation of NK cells versus T cells in the CRC tumor microenvironment. NK-cell migration into CRC tumor tissue is obviously impaired early during tumor development by mechanisms that do not affect T-cell infiltration. Clin Cancer Res; 17(4); 678–89. ©2011 AACR.</jats:p>
収録刊行物
-
- Clinical Cancer Research
-
Clinical Cancer Research 17 (4), 678-689, 2011-02-15
American Association for Cancer Research (AACR)