SP 7

Clinical significance of the local and systemic immunologic microenvironment in patients with colorectal cancer liver metastases

The detailed analysis of the immunological microenvironment and the involved immune cells in liver metastases of colorectal cancer has already yielded immunologically and clinically relevant insights (Halama et al. Cancer Res 2011 and Halama et al. Clin Cancer Res 2011). Especially for the prognostic evaluation and for treatment decisions, further analyses of the immunological microenvironment are promising. In this project, the developed technologies will be used to generate a comprehensive view on the local tissue immune parameters (i.e. immune cells, cytokines & chemokines in the tumor and in the adjacent liver) in combination with the systemic immune status, i.e. specific antibody responses and cytokines in the corresponding patient’s serum. Bringing together these compartments will show their associations, subsequently leading toward the identification of clinically relevant markers. This project clearly focuses on the detailed and integrative analysis of the immunological parameters in metastasized colorectal cancer patients.

Team SP 7
Dr. phil. nat. I. Zoernig, Dr. med. N. Halama, Prof. Dr. med. D. Jäger, J. Funk, A. Spille, T. Lerchl

Dr. phil. nat. I. Zoernig, Dr. med. N. Halama

Project-related key publications:

Keim S, Zoernig I, Spille A, Lahrmann B, Brand K, Herpel E, Grabe N, Jäger D, Halama N. Sequential metastases of colorectal cancer: Immunophenotypes and spatial distributions of infiltrating immune cells in relation to time and treatments. Oncoimmunology. 2012 Aug 1;1(5):593-599.

Halama N, Zoernig I, Grabe N, Jaeger D. The local immunological microenvironment in colorectal cancer as a prognostic factor for treatment decisions in the clinic: The way ahead. Oncoimmunology. 2012 Jan 1;1(1):62-66.

Lahrmann B, Halama N, Sinn HP, Schirmacher P, Jaeger D, Grabe N. Automatic tumor-stroma separation in fluorescence TMAs enables the quantitative high-throughput analysis of multiple cancer biomarkers. PLoS One. 2011;6(12):e28048.

Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, Pommerencke T, von Knebel DM, Folprecht G, Luber B, Feyen N, Martens UM, Beckhove P, Gnjatic S, Schirmacher P, Herpel E, Weitz J, Grabe N, Jaeger D. Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases Are Prognostic for Response to Chemotherapy. Cancer Res 2011, 71: 5670-5677.

Halama N, Braun M, Kahlert C, Spille A, Quack C, Rahbari N, Koch M, Weitz J, Kloor M, Zoernig I, Schirmacher P, Brand K, Grabe N, Falk CS. Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines. Clin Cancer Res 2011, 17: 678-689.

Gnjatic S, Ritter E, Buchler MW, Giese NA, Brors B, Frei C, Murray A, Halama N, Zoernig I, Chen YT, Andrews C, Ritter G, Old LJ, Odunsi K, Jager D. Seromic profiling of ovarian and pancreatic cancer. Proc Natl Acad Sci U S A 2010, 107: 5088-5093.

Halama N, Zoernig I, Spille A, Michel S, Kloor M, Grauling-Halama S, Westphal K, Schirmacher P, Jaeger D, Grabe N. Quantification of prognostic immune cell markers in colorectal cancer using whole slide imaging tumor maps. Anal Quant Cytol Histol 2010, 32: 333-340.

Lahrmann B, Halama N, Westphal K, Ernst C, Elsawaf Z, Sinn P, Bosch FX, Dickhaus H, Jager D, Schirmacher P, Grabe N. Robust gridding of TMAs after whole-slide imaging using template matching. Cytometry A 2010 Dec;77(12):1169-76. doi: 10.1002/cyto.a.20949.

Halama N, Michel S, Kloor M, Zoernig I, Pommerencke T, von Knebel Doeberitz M, Schirmacher P, Weitz J, Grabe N, Jager D. The localization and density of immune cells in primary tumors of human metastatic colorectal cancer shows an association with response to chemotherapy. Cancer Immun 2009 Feb 19;9:1.

Halama N, Zoernig I, Spille A, Westphal K, Schirmacher P, Jaeger D, Grabe N. Estimation of Immune Cell Densities in Immune Cell Conglomerates: An Approach for High-Throughput Quantification. PLoS One 2009 Nov 16;4(11):e7847. doi: 10.1371/journal.pone.0007847.

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