KFO 337

Welcome to the Clinical Research Unit "Phenotypic Therapy and Immune Escape in Cancer" (KFO 337 PhenoTImE)

The cure of cancer patients is still hampered by the resistance of tumor cells against drugs and the immune system. These phenomena point to a new understanding of cancer as a highly plastic system, in which cell populations switch into each other depending on the current therapeutic, microenvironmental, and immunological context. The novel approach of PhenoTImE is to collaboratively unravel the molecular circuitries that control this dynamic switching towards resistant phenotypes and the reciprocal interaction with the immune system.
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Spokesman

Prof. Dr. Dirk Schadendorf

Research Coordinator

Prof. Dr. Alexander Roesch

Administrative Coordinator

Dr. Astrid Hensel

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Save the dateInternational Symposium „Phenotypic Therapy and Immune Escape in Cancer“

Clinical Research Unit 337 – PhenoTImE
Thursday, 16 January 2025


Symposium Venue:
FUNKE Event-Center,
Essen Jakob-Funke-Platz 1, 45127 Essen

You can register here (Participation is free, but registration is mandatory).

Guest Speakers & Program
 

Selected Publications

Cibir Z, Hassel J, Sonneck J, Kowitz L, Beer A, Kraus A, Hallekamp G, Rosenkranz M, Raffelberg P, Olfen S, Smilowski K, Burkard R, Helfrich I, Tuz AA, Singh V, Ghosh S, Sickmann A, Klebl AK, Eickhoff JE, Klebl B, Seidl K, Chen J, Grabmaier A, Viga R, Gunzer M. ComplexEye: a multi-lens array microscope for high-throughput embedded immune cell migration analysis. Nat Commun. 2023 Dec 11;14(1):8103. doi: 10.1038/s41467-023-43765-3. PMID: 38081825; PMCID: PMC10713721.

Reissig TM, Tzianopoulos I, Liffers ST, Rosery VK, Guyot M, Ting S, Wiesweg M, Kasper S, Meister P, Herold T, Schmidt HH, Schumacher B, Albers D, Markus P, Treckmann J, Schuler M, Schildhaus HU, Siveke JT. Smaller panel, similar results: genomic profiling and molecularly informed therapy in pancreatic cancer. ESMO Open. 2023 Jun;8(3):101539. doi: 10.1016/j.esmoop.2023.101539.

Stupia S, Heeke C, Brüggemann A, Zaremba A, Thier B, Kretz J, Sucker A, Philip M, Zelinskyy G, Ferrone S, Roesch A, Horn S, Hadaschik E, Schadendorf D, Trilling M, Dittmer U, Griewank K, Zhao F, Paschen A. HLA Class II Loss and JAK1/2 Deficiency Coevolve in Melanoma Leading to CD4 T-cell and IFNγ Cross- Resistance. Clin Cancer Res 2023 Aug 1;29(15):2894-2907. doi: 10.1158/1078-0432.CCR-23-0099.

Váraljai R, Zimmer L, Al-Matary Y, Kaptein P, Albrecht LJ, Shannan B, Brase JC, Gusenleitner D, Amaral T, Wyss N, Utikal J, Flatz L, Rambow F, Reinhardt HC, Dick J, Engel DR, Horn S, Ugurel S, Sondermann W, Livingstone E, Sucker A, Paschen A, Zhao F, Placke JM, Klose JM, Fendler WP, Thommen DS, Helfrich I, Schadendorf D, Roesch A. Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma. Nat Cancer. 2023 Sep;4(9):1292-1308. doi: 10.1038/s43018-023-00610-2.

Albrecht LJ, Höwner A, Griewank K, Lueong SS, von Neuhoff N, Horn PA, Sucker A, Paschen A, Livingstone E, Ugurel S, Zimmer L, Horn S, Siveke JT, Schadendorf D, Váraljai R, Roesch A. Circulating cell-free messenger RNA enables non-invasive pan-tumour monitoring of melanoma therapy independent of the mutational genotype. Clin Transl Med. 2022 Nov;12(11):e1090. doi: 10.1002/ctm2.1090.

Brase JC, Walter RFH, Savchenko A, Gusenleitner D, Garrett J, Schimming T, Varaljai R, Castelletti D, Kim J, Dakappagari N, Schultz K, Robert C, Long GV, Nathan PD, Ribas A, Flaherty KT, Karaszewska B, Schachter J, Sucker A,..., Schadendorf D, Roesch A. Role of Tumor Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib. Clin Cancer Res, 27(16), 4500-4510. doi: 10.1158/1078-0432.CCR-20-3586.

Chauvistré H, Shannan B, Daignault-Mill SM, Ju RJ, Picard D, Egetemaier S, Váraljai R, Gibhardt CS, Sechi A, Kaschani F, Keminer O, Stehbens SJ, Liu Q, Yin X, Jeyakumar K, Vogel FCE, Krepler C, Rebecca VW, Kubat L,..., Schadendorf D, Roesch A. Persister state-directed transitioning and vulnerability in melanoma. Nat Commun. 2022 Jun 1;13(1):3055. doi: 10.1038/s41467-022-30641-9.

Harbers FN, Thier B, Stupia S, Zhu S, Schwamborn M, Peller V, Chauvistré H, Crivello P, Fleischhauer K, Roesch A, Sucker A, Schadendorf D, Chen Y, Paschen A, Zhao F. Melanoma Differentiation Trajectories Determine Sensitivity toward Pre-Existing CD8+ Tumor-Infiltrating Lymphocytes. J Invest Dermatol. 2021 Oct;141(10):2480-2489. doi: 10.1016/j.jid.2021.03.013.

Kebir S, Ullrich V, Berger P, Dobersalske C, Langer S, Rauschenbach L, Trageser D, Till A, Lorbeer FK, Wieland A, Wilhelm-Buchstab T, Ahmad A, Fröhlich H, Cima I, Prasad S, Matschke J, Jendrossek V, Remke M, Grüner BM, Roesch A,..., Scheffler B. A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma. Clin Cancer Res. 2023 Jan 17;29(2):488-500. doi: 10.1158/1078-0432.CCR-22-0611.

Liu D, Schilling B, Liu D, Sucker A, Livingstone E, Jerby-Arnon L, Zimmer L, Gutzmer R, Satzger I, Loquai C, Grabbe S, Vokes N, Margolis CA, Conway J, He MX, Elmarakeby H, Dietlein F, Miao D, Tracy A, ..., Schadendorf D. Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma. Nat Med. 2019 Dec;25(12):1916-1927. doi: 10.1038/s41591-019-0654-5.

Metzenmacher M, Váraljai R, Hegedüs B, Cima I, Forster J, Schramm A, Scheffler B, Horn PA, Klein CA, Szarvas T, Reis H, Bielefeld N, Roesch A, Aigner C, Kunzmann V, Wiesweg M, Siveke JT, Schuler M, Lueong SS. Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer. Cancers (Basel). 2020 Feb 4;12(2):353. doi: 10.3390/cancers12020353.

Such L, Zhao F, Liu D, Thier B, Le-Trilling VTK, Sucker A, Coch C, Pieper N, Howe S, Bhat H, Kalkavan H, Ritter C, Brinkhaus R, Ugurel S, Köster J, Seifert U, Dittmer U, Schuler M, Lang KS, Kufer TA, Hartmann G, Becker JC, Horn S, Ferrone S, Liu D, Van Allen EM, Schadendorf D, Griewank K, Trilling M, Paschen A. Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy. J Clin Invest. 2020 Aug 3;130(8):4266-4281. doi: 10.1172/JCI131572.

Thier B, Zhao F, Stupia S, Brüggemann A, Koch J, Schulze N, Horn S, Coch C, Hartmann G, Sucker A, Schadendorf D, Paschen A. Innate immune receptor signaling induces transient melanoma dedifferentiation while preserving immunogenicity. J Immunother Cancer. 2022 Jun;10(6):e003863. doi: 10.1136/jitc-2021-003863.

Váraljai R, Elouali S, Lueong SS, Wistuba-Hamprecht K, Seremet T, Siveke JT, Becker JC, Sucker A, Paschen A, Horn PA, Neyns B, Weide B, Schadendorf D, Roesch A. The predictive and prognostic significance of cell-free DNA concentration in melanoma. J Eur Acad Dermatol Venereol. 2021 Feb;35(2):387-395. doi: 10.1111/jdv.16766.

Váraljai R, Horn S, Sucker A, Piercianek D, Schmitt V, Carpinteiro A, Becker KA, Reifenberger J, Roesch A, Felsberg J, Reifenberger G, Sure U, Schadendorf D, Helfrich I. Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma. Cancers (Basel). 2021 Feb10;13(4):731. doi: 10.3390/cancers13040731.

Vogel FCE, Bordag N, Zügner E, Trajkovic-Arsic M, Chauvistré H, Shannan B, Váraljai R, Horn S, Magnes C, Thomas Siveke J, Schadendorf D, Roesch A. Targeting the H3K4 Demethylase KDM5B Reprograms the Metabolome and Phenotype of Melanoma Cells. J Invest Dermatol. 2019 Dec;139(12):2506-2516.e10. doi:10.1016/j.jid.2019.06.124.

Zhang X, Zegar T, Weiser T, Hamdan FH, Berger BT, Lucas R, Balourdas DI, Ladigan S, Cheung PF, Liffers ST, Trajkovic-Arsic M, Scheffler B, Joerger AC, Hahn SA, Johnsen SA, Knapp S, Siveke JT. Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma. Int J Cancer. 2020 Nov 15;147(10):2847-2861. doi: 10.1002/ijc.33137.