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 – Postdoc
• Saskia Stange, M. Sc - PhD student
• Julian Hlawatsch, MD student
• Marta Maccari, MS (visiting scientist)
• With support of the IMU team

• Safi S, Krzykalla J, Hoffmann H, Benner A, Bischoff H, Eichhorn M, Kriegsmann M, Poschke I, Stögbauer F, Umansky L, Mogler C, Weichert W, Winter H, Beckhove P, Muley T. Low tumor interleukin-1β expression predicts a limited effect of adjuvant platinum-based chemotherapy for patients with completely resected lung adenocarcinoma: An identification and validation study. Pulmonology. 2024. 
• Tan CL, Lindner K, Boschert T, Meng Z, Rodriguez Ehrenfried A, De Roia A, Haltenhof G, Faenza A, Imperatore F, Bunse L, Lindner JM, Harbottle RP, Ratliff M, Offringa R, Poschke I, Platten M, Green EW. Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy. Nat Biotechnol. 2024
• Boschert T, Kromer K, Lerner T, Lindner K, Haltenhof G, Tan CL, Jähne K, Poschke I, Bunse L, Eisele P, Grassl N, Mildenberger I, Sahm K, Platten M, Lindner JM, Green EW. H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient. Sci Adv, 2024
• Meyer M, Parpoulas C, Barthélémy T, Becker JP, Charoentong P, Lyu Y, Börsig S, Bulbuc N, Tessmer C, Weinacht L, Ibberson D, Schmidt P, Pipkorn R, Eichmüller SB, Steinberger P, Lindner K, Poschke I, Platten M, Fröhling S, Riemer AB, Hassel JC, Roberti MP, Jäger D, Zörnig I, Momburg F. MediMer: a versatile do-it-yourself peptide-receptive MHC class I multimer platform for tumor neoantigen-specific T cell detection. Front Immunol. 2024
• Grassl N, Sahm K, Süße H, Poschke I, Bunse L, Bunse T, Boschert T, Mildenberger I, Rupp AK, Ewinger MP, Lanz LM, Denk M, Tabatabai G, Ronellenfitsch MW, Herrlinger U, Glas M, Krex D, Vajkoczy P, Wick A, Harting I, Sahm F, von Deimling A, Bendszus M, Wick W, Platten M. INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. Neurol Res Pract. 2023
• Grassl N, Poschke I, Lindner K, Bunse L, Mildenberger I, Boschert T, Jähne K, Green EW, Hülsmeyer I, Jünger S, Kessler T, Suwala AK, Eisele P, Breckwoldt MO, Vajkoczy P, Grauer OM, Herrlinger U, Tonn JC, Denk M, Sahm F, Bendszus M, von Deimling A, Winkler F, Wick W, Platten M, Sahm K. A H3K27M-targeted vaccine in adults with diffuse midline glioma. Nat Med. 2023
• Lu KH, Michel J, Kilian M, Aslan K, Qi H, Kehl N, Jung S, Sanghvi K, Lindner K, Zhang XW, Green EW, Poschke I, Ratliff M, Bunse T, Sahm F, von Deimling A, Wick W, Platten M, Bunse L.
  T cell receptor dynamic and transcriptional determinants of T cell expansion in glioma-infiltrating T cells.
  Neurooncol Adv. 2022 Aug 31
• Liebers N, Speer C, Benning L, Bruch PM, Krämer I, Meissner J, Schnitzler P, Kräusslich HG, Dreger P, Müller-Tidow C, Poschke I, Dietrich S. Humoral and cellular responses after COVID-19 vaccination in anti-CD20 treated lymphoma patients. Blood. 2021 published online 10/2021
• Platten M, Bunse L, Wick A, Bunse T, Le Cornet L, Harting I, Sahm F, Sanghvi K, Tan CL, Poschke I, Green E, Justesen S, Behrens GA, Breckwoldt M, Freitag A, Rother LM, Schmitt A, Schnell O, Hense J, Misch M, Krex D, Stevanovic S, Tabatabai G, Steinbach JP, Bendszus M, von Deimling A, Schmitt M, Wick W. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature. (2021)
• van Tilburg CM, Witt R, Heiss M, Pajtler KW, Plass C, Poschke I, Platten M, Harting I, Sedlaczek O, Freitag A, Meyrath D, Taylor L, Balasubramanian GP, Jäger N, Pfaff E, Jones BC, Milde T, Pfister SM, Jones DTW, Kopp-Schneider A, Witt O.
  INFORM2 NivEnt: The first trial of the INFORM2 biomarker driven phase I/II trial series: the combination of nivolumab and entinostat in children and adolescents with refractory high-risk malignancies.
  BMC Cancer. 2020 Jun 5;20(1):523.
• Poschke IC, Hassel JC, Rodriguez-Ehrenfried A, Lindner KAM, Heras-Murillo I, Appel LM, Lehmann J, Lövgren T, Wickström SL, Lauenstein C, Roth J, König AK, Haanen JBAG, van den Berg J, Kiessling R, Bergmann F, Flossdorf M, Strobel O, Offringa R.
  The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones.
  Clin Cancer Res. 2020 Aug 15;26(16):4289-4301. Epub 2020 Apr 17.
• 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