Clinical Cooperation Unit Applied Tumor-Immunity

Prof. Dr. Dirk Jäger

CD3 positive T cells (brown) at the invasive margin of a Colorectal Cancer Liver Metastasis.
© dkfz.de

The research team of the Clinical Collaboration Unit “Applied Tumor Immunity” headed by Dirk Jäger focuses on the development of advanced analytical methods to characterize tumor host interactions in the immunological tumor microenvironment and the periphery. In particular, whole-slide imaging of histological sections coupled with automatic image processing, laser microdissection and multiplex protein quantification technologies as well as multiplex serological assays have been established. The goal is a comprehensive mechanistic analysis of immunological pathomechanisms in the tumor microenvironment and to develop individualized immunological therapy approaches that are then translated into clinical care of individual patients. Recently, Dirk Jäger’s group could show in metastatic colorectal cancer, initially in preclinical human tissue models as well as a phase I clinical trial that CCR5 inhibition induced a dramatic change of the environment towards a more T cell friendly environment, with redistribution of T cells, repolarization of M2 macrophages towards M1 macrophages and regression of metastatic lesions in chemotherapy refractory CRC patients (Halama et al., Cancer Cell 2016). In order to further support these developments of individualized immunological therapies the platforms Digital Tumor Tissue Computation (DTC) and Intratumoral Immunomonitoring have been established at NCT in close cooperation with Dirk Jäger’s group. As the Department of Medical Oncology is the main unit for cancer patient care at the NCT, the direct link between research in the Clinical Cooperation Unit and translation into clinical trials and care is highly efficient.

FUTURE OUTLOOK
The future goal of this Clinical Cooperation Unit is to develop and apply powerful tools to better stratify patients, analyze the microenvironment, and offer tailored treatments for individual patients. Further development of advanced technologies will allow an unparalleled insight into the makeup of the immunological pathomechanisms in serum samples, archival and fresh cancer specimens, as well as in new non-rodent explant models from patients. Extending immunological data sets by analyzing the mutational repertoire of tumors will improve our understanding of cancer at different levels.

Contact

Prof. Dr. Dirk Jäger
Applied Tumor-Immunity (D120)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 460
69120 Heidelberg
Tel: +49 6221 56 7228

Selected Publications

  • N. Halama, I. Zoernig, A. Berthel, C. Kahlert, F. Klupp, M. Suarez-Carmona, T. Suetterlin, K. Brand, J. Krauss, F. Lasitschka, T. Lerchl, C. Luckner-Minden, A. Ulrich, M. Koch, J. Weitz, M. Schneider, M. W. Buechler, L. Zitvogel, T. Herrmann, A. Benner, C. Kunz, S. Luecke, C. Springfeld, N. Grabe, C. S. Falk and D. Jaeger. Tumoral immune cell exploitation in colorectal cancer liver metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell, Cancer Cell. 29(4):587-601 (2016)
  • I. Zörnig, N. Halama, J. Lorenzo Bermejo, C. Ziegelmeier, E. Dickes, A. Migdoll, I. Kaiser, T. Waterboer, M. Pawlita, N. Grabe, S. Ugurel, D. Schadendorf, C. Falk, S. B. Eichmueller, D. Jaeger. Prognostic Significance of Spontaneous Antibody Responses against Tumor-Associated Antigens in Malignant Melanoma Patients. Int J Cancer. 136: 138-51 (2015)
  • F. Klug, H. Prakash, P.E. Huber, T. Seibel, N. Bender, N. Halama, C. Pfirschke, R.H. Voss, C. Timke, L. Umansky, K. Klapproth, K. Schäkel, N. Garbi, D. Jäger, J. Weitz, H. Schmitz-Winnenthal, G.J. Hämmerling, P. Beckhove. Low-dose irradiation programs macrophage differentiation to an iNOS?/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 24(5):589-602 (2013)
  • N. Halama, S. Michel, M. Kloor, I. Zoernig, A. Benner, A. Spille, T. Pommerencke, M. v Knebel Doeberitz, G. Folprecht, B. Luber, N. Feyen, U. M. Martens, P. Beckhove, S. Gnjatic, P. Schirmacher, E. Herpel, J. Weitz, N. Grabe and D. Jäger. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 71 (17):5670-7 (2011)
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