Immune monitoring and TCR discovery

The immune monitoring unit is located at the NCT and analyzes samples from cancer patients of various entities enrolled in clinical trials. We are specialized in monitoring antigen specific adaptive immune responses and contribute to a number of phase I and phase II clinical trials in Heidelberg, across Germany, as well as to multinational trials.

In order to maximize the knowledge gained from clinical samples, we aim to decipher characteristics of successful T cell responses that enable effective immunotherapy, or that are induced during the course of an immunological intervention. We are particularly interested to understand T cell receptor (TCR) repertoire composition and dynamics, its change during treatment and the hallmarks of T cells carrying tumor-antigen specific receptors. As part of these efforts, we work towards a warehouse of tumor-reactive TCRs, both shared- and unique-neoantigen-specific, that could be applied therapeutically. This project focuses on samples of patients with brain tumors, either as primary tumor site or as site of metastasis from other solid tumor entities.

• Isabel Poschke, PhD - Team leader
• Katharina Lindner, M.Sc – PhD student
• With support of the IMU team

• Wickström SL, Lövgren T, Volkmar M, Reinhold B, Duke-Cohan JS, Hartmann L, Rebmann J, Mueller A, Melief J, Maas R, Ligtenberg M, Hansson J, Offringa R, Seliger B, Poschke I, Reinherz EL, Kiessling R. Cancer Neoepitopes for Immunotherapy: Discordance Between Tumor-Infiltrating T Cell Reactivity and Tumor MHC Peptidome Display. Front Immunol. 2019 
• Buhl JL, Selt F, Hielscher T, Guiho R, Ecker J, Sahm F, Ridinger J, Riehl D, Usta D, Ismer B, Sommerkamp AC, Martinez-Barbera JP, Wefers AK, Remke M, Picard D, Pusch S, Gronych J, Oehme I, van Tilburg CM, Kool M, Kuhn D, Capper D, von Deimling A, Schuhmann MU, Herold-Mende C, Korshunov A, Brummer T, Pfister SM, Jones DTW, Witt O, Milde T. The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma. Clin Cancer Res. 2019
• Safi S, Yamauchi Y, Stamova S, Rathinasamy A, Op den Winkel J, Jünger S, Bucur M, Umansky L, Warth A, Herpel E, Eichhorn M, Winter H, Hoffmann H, Beckhove P. Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer. Oncoimmunology. 2019 
• Ge Y, Böhm HH, Rathinasamy A, Xydia M, Hu X, Pincha M, Umansky L, Breyer C, Hillier M, Bonertz A, Sevko A, Domschke C, Schuetz F, Frebel H, Dettling S, Herold-Mende C, Reissfelder C, Weitz J, Umansky V, Beckhove P. Tumor-Specific Regulatory T Cells from the Bone Marrow Orchestrate Antitumor Immunity in Breast Cancer. Cancer Immunol Res. 2019 
• Platten M, Schilling D, Bunse L, Wick A, Bunse T, Riehl D, Karapanagiotou-Schenkel I, Harting I, Sahm F, Schmitt A, Steinbach J, Weyerbrock A, Hense J, Misch M, Krex D, Stevanović S, Tabatabai G, von Deimling A, Schmitt M, Wick W. A mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group (NOA-16). Oral presentation at the Annual ASCO Conference. 2018
• Wabnitz GH, Kirchgessner H, Jahraus B, Umansky L, Shenolikar S, Samstag Y. Protein Phosphatase 1αand Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells. Mol Cell Biol. 2018
• Yamauchi Y, Safi S, Blattner C, Rathinasamy A, Umansky L, Juenger S, Warth A, Eichhorn M, Muley T, Herth FJF, Dienemann H, Platten M, Beckhove P, Utikal J, Hoffmann H, Umansky V. Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non-Small Cell Lung Cancer. Am J Respir Crit Care Med. 2018
• Platten M, Bunse L, Riehl D, Bunse T, Ochs K, Wick W. Vaccine Strategies in Gliomas. Curr Treat Options Neurol. 2018 
• Haag GM, Zoernig I, Hassel JC, Halama N, Dick J, Lang N, Podola L, Funk J, Ziegelmeier C, Juenger S, Bucur M, Umansky L, Falk CS, Freitag A, Karapanagiotou-Schenkel I, Beckhove P, Enk A, Jaeger D. Phase II trial of ipilimumab in melanoma patients with preexisting humoural immune response to NY-ESO-1. Eur J Cancer. 2018 
• Schmitz-Winnenthal FH, Hohmann N, Schmidt T, Podola L, Friedrich T, Lubenau H, Springer M, Wieckowski S, Breiner KM, Mikus G, Büchler MW, Keller AV, Koc R, Springfeld C, Knebel P, Bucur M, Grenacher L, Haefeli WE, Beckhove P. A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGFR2, in patients with advanced pancreatic cancer. Oncoimmunology. 2018 
• Rapp C, Warta R, Stamova S, Nowrouzi A, Geisenberger C, Gal Z, Roesch S, Dettling S, Juenger S, Bucur M, Jungk C, DaoTrong P, Ahmadi R, Sahm F, Reuss D, Fermi V, Herpel E, Eckstein V, Grabe N, Schramm C, Weigand MA, Debus J, von Deimling A, Unterberg A, Abdollahi A, Beckhove P, Herold-Mende C. Identification of T cell target antigens in glioblastoma stem-like cells using an integrated proteomics-based approach in patient specimens. Acta Neuropathol. 2017 
• Rathinasamy A, Domschke C, Ge Y, Böhm HH, Dettling S, Jansen D, Lasitschka F, Umansky L, Gräler MH, Hartmann J, Herold-Mende C, Schuetz F, Beckhove P. Tumor specific regulatory T cells in the bone marrow of breast cancer patients selectively upregulate the emigration receptor S1P1. Cancer Immunol Immunother. 2017
• Poschke I, Flossdorf M, Offringa R. Next-generation TCR sequencing - a tool to understand T-cell infiltration in human cancers. J Pathol. 2016 
• Poschke I, Faryna M, Bergmann F, Flossdorf M, Lauenstein C, Hermes J, Hinz U, Hank T, Ehrenberg R, Volkmar M, Loewer M, Glimm H, Hackert T, Sprick MR, Höfer T, Trumpp A, Halama N, Hassel JC, Strobel O, Büchler M, Sahin U, Offringa R. Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma. Oncoimmunology. 2016 
• Miyan M, Schmidt-Mende J, Kiessling R, Poschke I, de Boniface J. Differential tumor infiltration by T-cells characterizes intrinsic molecular subtypes in breast cancer. J Transl Med. 2016 
• Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, Holland-Letz, T., Umansky L, Beckhove P, Sucker A, Schadendorf D, Utikal J, Umansky V. Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab. Clin. Cancer Res. 2015
• Schneider T, Sevko A, Heussel CP, Umansky L, Beckhove P, Dienemann H, Safi S, Utikal J, Hoffmann H, Umansky V. Serum inflammatory factors and circulating immunosuppressive cells are predictive markers for efficacy of radiofrequency ablation in non-small cell lung cancer. Clin Exp Immunol. 2015
• Schmitz-Winnenthal FH, Hohmann N, Niethammer AG, Friedrich T, Lubenau H, Springer M, Breiner KM, Mikus G, Weitz J, Ulrich A, Buechler MW, Pianka F, Klaiber U, Diener M, Leowardi C, Schimmack S, Sisic L, Keller AV, Koc R, Springfeld C, Knebel P, Schmidt T, Ge Y, Bucur M, Stamova S, Podola L, Haefeli WE, Grenacher L, Beckhove P. Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial. Oncoimmunology. 2015