Mechanisms of immune evasion caused by aberrant innate nucleic acid receptor signaling in tumor cells and their tumor microenvironment


Project Summary

Type I interferons (IFN-I) induced by innate immune signaling pathways in immune and tumor cells are emerging as intriguing determinants of both anti-melanoma responses as well as immune escape and resistance mechanisms. In this proposal, we aim to understand the distinct contribution of IFN-I inducing nucleic acid receptor pathways in tumor and host cells during development and immunosurveillance of melanoma as well as to identify the mechanisms that drive disease resistance.

The scientific work of Professor Dr. Hendrik Poeck, Senior Physician in charge of the Clinic and Polyclinic for Internal Medicine III of the University Hospital Regensburg (UKR), is funded as part of the newly established excellence program of the German Cancer Aid (DKH).

On February 1, 2020, Hendrik Poeck accepted the call to the W2 professorship for internal medicine with a focus on stem cell transplantation and tumor immunology at the University of Regensburg.

The aim of immunotherapies is to enable the immune system once again to fight cancer on its own. Drugs known as checkpoint inhibitors are already in clinical use for this purpose. However, they are only effective in about one third of patients.

Thiele Orberg, E., Meedt, E., Hiergeist, A., Xue, J., Heinrich, P., Ru, J., Ghimire, S., Miltiadous, O., Lindner, S., Tiefgraber, M., Goldel, S., Eismann, T., Schwarz, A., Gottert, S., Jarosch, S., Steiger, K., Schulz, C., Gigl, M., Fischer, J.C., Janssen, K.P., Quante, M., Heidegger, S., Herhaus, P., Verbeek, M., Ruland, J., van den Brink, M.R.M., Weber, D., Edinger, M., Wolff, D., Busch, D.H., Kleigrewe, K., Herr, W., Bassermann, F., Gessner, A., Deng, L., Holler, E., Poeck, H. (2024). Nat Cancer.


Heidegger, S., Stritzke, F., Dahl, S., Dassler-Plenker, J., Joachim, L., Buschmann, D., Fan, K., Sauer, C.M., Ludwig, N., Winter, C., Enssle, S., Li, S., Perl, M., Gorgens, A., Haas, T., Orberg, E.T., Gottert, S., Wolfel, C., Engleitner, T., Cortes-Ciriano, I., Rad, R., Herr, W., Giebel, B., Ruland, J., Bassermann, F., Coch, C., Hartmann, G., Poeck, H. (2023). Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy. Cell Rep Med 4, 101171.

DOI: 10.1016/j.omto.2023.08.001

Jarosch, S., Köhlen, J., Ghimire, S., Orberg, E. T., Hammel, M., Gaag, D., Evert, M., Janssen, K. P., Hiergeist, A., Gessner, A., Weber, D., Meedt, E., Poeck, H., D'Ippolito, E., Holler, E. & Busch, D. H. (2023). Cell Rep Med, 4, 101125.


Stein-Thoeringer, C. K., Saini, N. Y., Zamir, E., Blumenberg, V., Schubert, M. L., Mor, U., Fante, M. A., Schmidt, S., Hayase, E., Hayase, T., Rohrbach, R., Chang, C. C., McDaniel, L., Flores, I., Gaiser, R., Edinger, M., Wolff, D., Heidenreich, M., Strati, P., Nair, R., Chihara, D., Fayad, L. E., Ahmed, S., Iyer, S. P., Steiner, R. E., Jain, P., Nastoupil, L. J., Westin, J., Arora, R., Wang, M. L., Turner, J., Menges, M., Hidalgo-Vargas, M., Reid, K., Dreger, P., Schmitt, A., Müller-Tidow, C., Locke, F. L., Davila, M. L., Champlin, R. E., Flowers, C. R., Shpall, E. J., Poeck, H., Neelapu, S. S., Schmitt, M., Subklewe, M., Jain, M. D., Jenq, R. R. & Elinav, E. (2023). Nat Med.


Fischer, J. C., Bscheider, M., Gottert, S., Thiele Orberg, E., Combs, S. E., Bassermann, F., Heidegger, S., Haas, T., Poeck, H. (2019). Sci Rep 9, 14955.

DOI:10.1038/s41598-019-51431-2(link is external)

Heidegger, S., Wintges, A., Stritzke, F., Bek, S., Steiger, K., Koenig, P. A., Gottert, S., Engleitner, T., Ollinger, R., Nedelko, T., Fischer, J. C., Makarov, V., Winter, C., Rad, R., van den Brink, M. R. M., Ruland, J., Bassermann, F., Chan, T. A., Haas, T., Poeck, H. (2019). Sci Immunol 4.

DOI:10.1126/sciimmunol.aau8943(link is external)

Heidegger, S., Kreppel, D., Bscheider, M., Stritzke, F., Nedelko, T., Wintges, A., Bek, S., Fischer, J.C., Graalmann, T., Kalinke, U., Bassermann, F., Haas, T., Poeck, H. (2019). EBioMedicine 41, 146-155.

DOI: 10.1016/j.ebiom.2019.02.056(link is external)

Muller, N., Fischer, J.C., Yabal, M., Haas, T., Poeck, H., Jost, P.J. (2019). Eur J Immunol 49, 504-507.

DOI: 10.1002/eji.201847818(link is external)

Bek, S., Stritzke, F., Wintges A., Nedelko, T., Böhmer, D.F.R.,  Fischer, J.C., Haas, T., Poeck, H., Heidegger, S. (2019). OncoImmunology 8, e1570779.

DOI: 10.1080/2162402X.2019.1570779(link is external)