Clinical Cooperation Unit Applied Tumor-Immunity

Prof. Dr. Dirk Jäger

CCR5 Blockade and Amelioration of the Tumor-Promoting Microenvironment in Human Cancer Patients Leads to Clinical Effects. Representative PET-MRI images from a patient receiving chemotherapy (CHT) after trial participation. White arrow indicates liver with metastatic lesions. Red spots indicate high glucose uptake typical for metastases, and green indicates low background glucose uptake.

To contribute to the goal of life without cancer, our team around Prof. Dr. Dirk Jäger, Dr. Niels Halama, and Dr. Inka Zörnig specializes in unleashing the full potential of the patient’s immune system to seek and destroy tumor cells. Due to the mutated nature of cancer cells and the resulting expression of neoantigens, these cells can potentially be detected by the immune system. However, as tumor cells present and secrete signals that create a microenvironment that can inhibit T cells from infiltrating and recognizing tumors, we explore and exploit various possibilities around checkpoint inhibition to neutralize the tumor’s immune-evading microenvironment, and have shown that combinatorial immunotherapies can lead to clinical responses in otherwise non-responders. We showed that T cells at invasive margins of human colorectal cancer (CRC) liver metastases produce CCL5, which has tumor-promoting effects on tumor cells and tumor-associated macrophages. CCR5 blockade mitigates the tumor-promoting microenvironment and leads to clinical responses in CRC patients (Halama et al., 2016).

We employ and develop advanced analytical methods to characterize tumor host interactions, including whole-slide imaging coupled with automatic image processing, laser microdissection, and multiplex proteomics technologies and develop drugs against novel immunological targets. Further, to determine the prognostic and predictive value of blood based biomarkers we established a platform for multiplex analysis of serum antibodies against tumor-associated antigens (Zörnig et al., 2015). Importantly, we also established a human tumor explant model in our lab, allowing safe testing of novel drugs and drug combinations (Halama et al., Cancer Cell 2016).

We are building on these promising technologies and findings and have initiated several clinical trials.

In order to provide true precision oncology we aim to better understand mechanisms of response and resistance in the individual patient, especially with respect to checkpoint inhibition. An essential tool to reach this goal are our human tumor explant models, allowing not only to molecularly understand the immediate effects of applied treatments but additionally allowing safe testing of novel drugs and drug combinations (Halama et al., Cancer Cell 2016). We will continue to employ and develop advanced analytical methods to characterize tumor-host interactions and will continue to initiate innovative clinical trials.


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

Selected Publications

  • Halama N. et al. (2016). Tumoral immune cell exploitation in colorectal cancer liver metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell, 29(4):587-60.
  • Zörnig I. et al. (2015). Prognostic Significance of Spontaneous Antibody Responses against Tumor-Associated Antigens in Malignant Melanoma Patients. Int J Cancer, 136: 138-5.
  • Krawczyk A. et al. (2013). Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody. Proc Natl Acad Sci U S A, 110(17):6760-5.
  • Klug F. et al. (2013). Low-dose irradiation programs macrophage differentiation to an iNOS?/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell, 24(5):589-602.
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