Team Heidelberg

Our group has pioneered research on the immune biology of Lynch syndrome-associated microsatellite-unstable (MSI) cancers. We started studying MSI cancer evolution more than 20 years ago  and described the major Darwinian selection principles in tumors and characterized possible immune evasion mechanisms. Our most recent research demonstrated the decisive role of the immune system in shaping tumor evolution, pointing particularly at the importance of individual’s HLA type for tumor immunoediting. Using this knowledge, we together with our collaboration partners now aim at linking individual’s HLA type to Lynch syndrome-associated cancer risk and tumor characteristics.

Ahadova A, Witt J, Haupt S, Gallon R, Hüneburg R, Nattermann J, Ten Broeke S, Bohaumilitzky L, Hernandez-Sanchez A, Santibanez-Koref M, Jackson MS, Ahtiainen M, Pylvänäinen K, Andini K, Grolmusz VK, Möslein G, Dominguez-Valentin M, Møller P, Fürst D, Sijmons R, Borthwick GM, Burn J, Mecklin JP, Heuveline V, von Knebel Doeberitz M, Seppälä T, Kloor M. Int J Cancer. Is HLA type a possible cancer risk modifier in Lynch syndrome? 2022 Oct 10. doi: 10.1002/ijc.34312. Online ahead of print.

Vaccines for immunoprevention of DNA mismatch repair deficient cancers. Alejandro Hernandez-Sanchez, Mark Grossman, Kevin Yeung, Shizuko S Sei, Steven Lipkin, Matthias Kloor. J Immunother Cancer. 2022 Jun;10(6):e004416.

Lena Bohaumilitzky, Klaus Kluck, Robert Hüneburg, Richard Gallon, Jacob Nattermann, Martina Kirchner, Glen Kristiansen, Oliver Hommerding, Pauline L Pfuderer, Lelia Wagner, Fabian Echterdiek, Svenja Kösegi, Nico Müller, Konstantin Fischer, Nina Nelius, Ben Hartog, Gillian Borthwick, Elena Busch, Georg Martin Haag, Hendrik Bläker, Gabriela Möslein, Magnus von Knebel Doeberitz, Toni T Seppälä, Maarit Ahtiainen, Jukka-Pekka Mecklin, D Timothy Bishop, John Burn, Albrecht Stenzinger, Jan Budczies, Matthias Kloor, Aysel Ahadova. The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients. Gastroenterology. 2022 Mar;162(3):907-919.e10.

Johannes Gebert, Ozkan Gelincik, Mine Oezcan-Wahlbrink, Jason D Marshall, Alejandro Hernandez-Sanchez, Katharina Urban, Mark Long, Eduardo Cortes, Elena Tosti, Eva M Katzenmaier, Yurong Song, Ali Elsaadi, Nan Deng, Eduardo Vilar, Vera Fuchs, Nina Nelius, Yan Yuan, Aysel Ahadova, Shizuko Sei, Robert H Shoemaker, Asad Umar, Lei Wei, Song Liu, Peer Bork, Winfried Edelmann, Magnus von Knebel Doeberitz, Steven M Lipkin, Matthias Kloor. Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model. Gastroenterology. 2021 Oct;161(4):1288-1302.

Saskia Haupt, Alexander Zeilmann, Aysel Ahadova, Hendrik Bläker, Magnus von Knebel Doeberitz, Matthias Kloor, Vincent Heuveline. Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure. PLoS Comput Biol. 2021 May 18;17(5):e1008970. eCollection 2021 May.

Aysel Ahadova, Pauline Luise Pfuderer, Maarit Ahtiainen, Alexej Ballhausen, Lena Bohaumilitzky, Svenja Kösegi, Nico Müller, Yee Lin Tang, Kosima Kosmalla, Johannes Witt, Volker Endris, Albrecht Stenzinger, Magnus von Knebel Doeberitz, Hendrik Bläker, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Mecklin, Toni T Seppälä, Matthias Kloor. Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance. J Clin Med. 2021 Jun 1;10(11):2458.

Sanne W Bajwa-Ten Broeke, Alexej Ballhausen, Aysel Ahadova, Manon Suerink, Lena Bohaumilitzky, Florian Seidler, Hans Morreau, Tom van Wezel, Julia Krzykalla, Axel Benner, Noel F de Miranda, Magnus von Knebel Doeberitz, Maartje Nielsen, Matthias Kloor. The coding microsatellite mutation profile of PMS2-deficient colorectal cancer. Exp Mol Pathol. 2021 Jul 21;104668. Online ahead of print.

Ballhausen A, Przybilla MJ, Jendrusch M, Haupt S, Pfaffendorf E, Seidler F, Witt J, Hernandez Sanchez A, Urban K, Draxlbauer M, Krausert S, Ahadova A, Kalteis MS, Pfuderer PL, Heid D, Stichel D, Gebert J, Bonsack M, Schott S, Bläker H, Seppälä T, Mecklin JP, Ten Broeke S, Nielsen M, Heuveline V, Krzykalla J, Benner A, Riemer AB, von Knebel Doeberitz M, Kloor M. The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution. Nat Commun. 2020 Sep 21;11(1):4740.

Bläker H, Haupt S, Morak M, Holinski-Feder E, Arnold A, Horst D, Sieber-Frank J, Seidler F, von Winterfeld M, Alwers E, Chang-Claude J, Brenner H, Roth W, Engel C, Löffler M, Möslein G, Schackert H-K, Weitz J, Perne C, Aretz S, Hüneburg R, Schmiegel W, Vangala D, Rahner N, Steinke-Lange V, Heuveline V, von Knebel Doeberitz M, Ahadova A, Hoffmeister M, Kloor M and the German Consortium for Familial Intestinal Cancer. Age-dependent performance of BRAF mutation testing in Lynch syndrome diagnostics. Int J Cancer. 2020 Nov 15;147(10):2801-2810.

Ahadova A, Seppälä TT, Engel C, Gallon R, Burn J, Holinski-Feder E, Steinke-Lange V, Möslein G, Nielsen M, Ten Broeke SW, Laghi L, Dominguez-Valentin M, Capella G, Macrae F, Scott R, Hüneburg R, Nattermann J, Hoffmeister M, Brenner H, Bläker H, von Knebel Doeberitz M, Sampson JR, Vasen H, Mecklin JP, Møller P, Kloor M. The “unnatural” history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance. Int J Cancer. 2021 Feb 15;148(4):800-811.

Kloor M, Reuschenbach M, Pauligk C, Karbach J, Rafiyan MR, Al-Batran SE, Tariverdian M, Jäger E, von Knebel Doeberitz M. A Frameshift Peptide Neoantigen-Based Vaccine for Mismatch Repair-Deficient Cancers: A Phase I/IIa Clinical Trial. Clin Cancer Res. 2020 Sep 1;26(17):4503-4510.

Bohaumilitzky L, von Knebel Doeberitz M, Kloor M, Ahadova A. Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review. J Clin Med. 2020 Jun 4;9(6):1741.

Engel C, Ahadova A, Seppälä T, Aretz S, Bigirwamungu-Bargeman M, Bläker H, Bucksch K, Büttner R, de Vos Tot Nederveen Cappel W, Endris V, Holinski-Feder E, Holzapfel S, Hüneburg R, Jacobs MAJM, Koornstra JJ, Langers AM, Lepistö A, Morak M, Möslein G, Peltomäki P, Pylvänäinen K, Rahner N, Renkonen-Sinisalo L, Schulmann K, Steinke-Lange V, Stenzinger A, Strassburg CP, van de Meeberg PC, van Kouwen M, van Leerdam M, Vangala DB, Vecht J, Verhulst ML, von Knebel Doeberitz M, Weitz J, Zachariae S, Loeffler M, Mecklin JP*, Kloor M*, Vasen HF*; German HNPCC Consortium, the Dutch Lynch Syndrome Collaborative Group, and the Finnish Lynch Syndrome Registry. Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome. Gastroenterology. 2020 Apr;158(5):1326-1333.