Home | Research | LIT Cooperation Groups | Transl. Immunobiology of Early Systemic Cancer Transl. Immunobiology of Early Systemic Cancer Research We investigate the early stages of metastasis, with a focus on the interaction of disseminated cancer cells (DCCs) with the immune microenvironment in key niches such as the bone marrow and lymph nodes. Using cutting-edge methods, including genome and transcriptome sequencing of rare cells from patient samples at single-cell resolution, as well as the use of PDX and humanized mouse models, we study how DCCs evade immune surveillance, alter their genome, and leverage phenotypic plasticity to adapt to new microenvironments and establish metastases. Our goal is to translate these findings into the development of innovative adjuvant immunotherapies capable of preventing metastatic growth. The Silent Struggle: Microenvironmental Control and Evolution of Metastasis-Initiating Disseminated Cancer Cells Themes and collaborations that drive us Publications Visit the complete publications list on Google Scholar: https://scholar.google.com/citations?hl=de&user=pAMiy0UAAAAJ Here is a selection of the most important publications from the last few years: Guetter, S., C., K., Koerkel-Qu, H., Markiewicz, A., Scheitler, S., Katzer, M., Berneburg, M., Renner, P., Cucuruz, B., Guttenberger, L., Naimer, V., Weidele, K., Treitschke, S., Werno, C., Jaser, H., Bargmann, T., Braun, A., Weber, F., Evert, K., Rochwarger, A., Schürch, C.M., Limm, K., Oefner, P.J., Rachel, R., Baumann, F., Warfsmann, J., Gütter, K., Mohammadi, P., Ulmer, A., Haferkamp, S., Klein, C.A., and Werner-Klein, M. (2025). MCSP+ metastasis founder cells activate immunosuppression early in human melanoma metastatic colonization. Nature Cancer. 10.1038/s43018-025-00963-w Treitschke, S., Weidele, K., Varadarajan, A.R., Feliciello, G., Warfsmann, J., Vorbeck, S., Polzer, B., Botteron, C., Hoffmann, M., Dechand, V., Mederer, T., Weber, F., Werner-Klein, M., Robold, T., Hofmann, H.S., Werno, C., and Klein, C.A. (2023). Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression. Int J Cancer 153, 1854-1867. 10.1002/ijc.34658. Sorrentino, A., Menevse, A.N., Michels, T., Volpin, V., Durst, F.C., Sax, J., Xydia, M., Hussein, A., Stamova, S., Spoerl, S., Heuschneider, N., Muehlbauer, J., Jeltsch, K.M., Rathinasamy, A., Werner-Klein, M., Breinig, M., Mikietyn, D., Kohler, C., Poschke, I., Purr, S., Reidell, O., Martins Freire, C., Offringa, R., Gebhard, C., Spang, R., Rehli, M., Boutros, M., Schmidl, C., Khandelwal, N., and Beckhove, P. (2022). Salt-inducible kinase 3 protects tumor cells from cytotoxic T-cell attack by promoting TNF-induced NF-kappaB activation. J Immunother Cancer 10. 10.1136/jitc-2021-004258. Tao, L., Raz, O., Marx, Z., Ghosh, M.S., Huber, S., Greindl-Junghans, J., Biezuner, T., Amir, S., Milo, L., Adar, R., Levy, R., Onn, A., Chapal-Ilani, N., Berman, V., Ben Arie, A., Rom, G., Oron, B., Halaban, R., Czyz, Z.T., Werner-Klein, M., Klein, C.A., and Shapiro, E. (2021). Retrospective cell lineage reconstruction in humans by using short tandem repeats. Cell Rep Methods 1, None. 10.1016/j.crmeth.2021.100054. Werner-Klein, M., Grujovic, A., Irlbeck, C., Obradovic, M., Hoffmann, M., Koerkel-Qu, H., Lu, X., Treitschke, S., Kostler, C., Botteron, C., Weidele, K., Werno, C., Polzer, B., Kirsch, S., Guzvic, M., Warfsmann, J., Honarnejad, K., Czyz, Z., Feliciello, G., Blochberger, I., Grunewald, S., Schneider, E., Haunschild, G., Patwary, N., Guetter, S., Huber, S., Rack, B., Harbeck, N., Buchholz, S., Rummele, P., Heine, N., Rose-John, S., and Klein, C.A. (2020). Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency. Nat Commun 11, 4977. 10.1038/s41467-020-18701-4. Yu, Y., Schleich, K., Yue, B., Ji, S., Lohneis, P., Kemper, K., Silvis, M.R., Qutob, N., van Rooijen, E., Werner-Klein, M., Li, L., Dhawan, D., Meierjohann, S., Reimann, M., Elkahloun, A., Treitschke, S., Dorken, B., Speck, C., Mallette, F.A., Zon, L.I., Holmen, S.L., Peeper, D.S., Samuels, Y., Schmitt, C.A., and Lee, S. (2018). Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma. Cancer Cell 33, 785. 10.1016/j.ccell.2018.03.009. Werner-Klein, M., Scheitler, S., Hoffmann, M., Hodak, I., Dietz, K., Lehnert, P., Naimer, V., Polzer, B., Treitschke, S., Werno, C., Markiewicz, A., Weidele, K., Czyz, Z., Hohenleutner, U., Hafner, C., Haferkamp, S., Berneburg, M., Rummele, P., Ulmer, A., and Klein, C.A. (2018). Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma. Nat Commun 9, 595. 10.1038/s41467-017-02674-y. Ulmer, A., Dietz, K., Werner-Klein, M., Hafner, H.M., Schulz, C., Renner, P., Weber, F., Breuninger, H., Rocken, M., Garbe, C., Fierlbeck, G., and Klein, C.A. (2018). The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival. Eur J Cancer 91, 1-10. 10.1016/j.ejca.2017.12.002. Hosseini, H., Obradovic, M.M.S., Hoffmann, M., Harper, K.L., Sosa, M.S., Werner-Klein, M., Nanduri, L.K., Werno, C., Ehrl, C., Maneck, M., Patwary, N., Haunschild, G., Guzvic, M., Reimelt, C., Grauvogl, M., Eichner, N., Weber, F., Hartkopf, A.D., Taran, F.A., Brucker, S.Y., Fehm, T., Rack, B., Buchholz, S., Spang, R., Meister, G., Aguirre-Ghiso, J.A., and Klein, C.A. (2016). Early dissemination seeds metastasis in breast cancer. Nature 540, 552-558. 10.1038/nature20785. Werner-Klein, M., Proske, J., Werno, C., Schneider, K., Hofmann, H.S., Rack, B., Buchholz, S., Ganzer, R., Blana, A., Seelbach-Gobel, B., Nitsche, U., Mannel, D.N., and Klein, C.A. (2014). Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients. PLoS One 9, e97860. 10.1371/journal.pone.0097860. Werner-Klein, M., Goggel, R., Westhof, A., and Erb, K.J. (2008). Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. Pulm Pharmacol Ther 21, 648-656. 10.1016/j.pupt.2008.03.002. Werner-Klein, M., Dresch, C., Marconi, P., and Brocker, T. (2007). Transcriptional targeting of B cells for induction of peripheral CD8 T cell tolerance. J Immunol 178, 7738-7746. 10.4049/jimmunol.178.12.7738. Funding Many thanks to the funding agencies who support our work: DFG – Deutsche Forschungsgemeinschaft https://www.dfg.de/en 2025-2027: Organ-defense and immune mechanisms determining the invisible phase of metastatic melanoma and breast cancer 2021-2024: Disseminated cancer cell-derived extracellular vesicles in early metastatic organ colonization TRR 305 2018-2021: Identification of tumor-cell intrinsic and microenvironmental factors influencing lymph node colonization in melanoma FOR2127 2017-2021: Identification of tumor-specific peptides for adjuvant immunotherapy of melanoma patients without distant metastasis 2009-2014: Etablierung eines humanisierten Tumor-Mausmodells DFG-Einzelantrag Hiege-Stiftung gegen Hautkrebs 2019-2021: Evaluation of diagnostic leukapheresis for the detection of circulating melanoma cells in minimal residual disease Wilhelm-Sander-Stiftung 2015-2018: Identification of prognostic markers by analysis of the functional stemcell phenotype in melanoma Contact & Lab Life Assoc. Prof. Dr. Melanie Werner-Klein Head of LIT Cooperation Group | Transl. Immunobiology of Early Systemic Cancer Tel: +49 941 944-11223 Email: melanie.werner-klein@ukr.de
