Despite high remission rates achieved with conventional chemotherapy in acute myeloid leukemia (AML), the risk of relapse remains substantial. This is partly due to a variety of molecular aberrations and immune deficiencies. The complex interplay between leukemic cells and their microenvironment — including various immune effector cells — plays a critical role in disease development and progression.

A key resource in our research is our institutional AML biobank, which provides high-quality, longitudinal samples of bone marrow, blood, and plasma from more than 700 well-characterized AML patients, enabling close integration of experimental findings with clinical data.

Flemming Bones (Medizindoktorand)
Dana Bui (Medizindoktorandin)
Dr. Sophia Cichutek (Ärztin)
Annika Dukek (BTA)
Nadine Felber (BTA)
Laura Holzapfel (Medizindoktorandin)
Moritz Kruppa (Medizindoktorand)
Niklas Kruppa (Medizindoktorand)
Rui Lu ((Medizindoktorandin)
Bente Meißner (BTA)
Jana Muschhammer(BTA)
Paul Opgenhoff (Medizindoktorand)
Talika Pommerencke (Medizindoktorandin)
Jule Pröhl (Medizindoktorandin)
Dr. Azam Salimi (Postdoc)
Elisa Seubert (Ärztin)
Leticia Souza (naturwissenschaftliche Doktorandin)
Lisa Truong (Medizindoktorandin)
Greta Weber (Medizindoktorandin)
Dr. Clara Wienecke (Ärztin)

Senior Scientific Advisor

Prof. Dr. med. Walter Fiedler

I. Cancer immunology

Numerous studies have already shown initial success with immunological therapy approaches for tumors. The successful results of allogeneic stem cell transplantation have confirmed the success of immunotherapeutic strategies for AML. However, due to its severe side effects and the often advanced age of AML patients, this treatment option is only suitable for some patients, meaning that new immunotherapeutic strategies must be developed and evaluated to offer potent alternatives. Cancer cells can escape the immune system by acquiring immunosuppressive mechanisms. Our team is focused on the development and validation of antibody-based immunotherapeutic strategies to reactivate effector cells of the adaptive and innate immune system and to block characteristic immune-exhaustion patterns that enable tumor progression. We could recently show that single or multi-specific blockade of inhibitory receptors and/or ectoenzymes expressed by αβ-T cells, NK cells and macrophages enhances activation, proliferation and cytotoxicity of those immune cells. We develop immunotherapeutic strategies for malignant neoplasia with a special focus on acute myeloid leukemia but also in the fields of multiple myeloma, high grade ovarian cancer, prostate cancer, and non-small cell lung cancer. We aim to understand the immunological mechanisms of action and resistance to identify predictive immunologic markers for selecting the appropriate immunotherapies and to identify suitable immunotherapeutic strategies for each individual patient.

II. Targeting the leukemic niche

The leukemia stem cell niche provides leukemia cells in the bone marrow with a specialized protective environment, shielding them from external stressors such as chemotherapy and immune-mediated attack. This protective interaction contributes significantly to the persistence of minimal residual disease and is a key factor underlying the high relapse rates observed in patients with acute myeloid leukemia. The complex interactions between leukemia cells and stromal components are still only partially understood. To address this, our research group systematically investigates cellular and molecular communication within the leukemic niche, with particular emphasis on the interaction between AML blasts and stromal cells, including mesenchymal stromal cells (MSCs) and endothelial cells (ECs). By characterizing these interactions, we aim to identify key pathways that contribute to leukemic cell survival, immune evasion, and therapy resistance. Our translational approach combines patient-derived samples with advanced co-culture systems, molecular profiling and mouse models to uncover novel targets for therapeutic intervention. Ultimately, this strategy enables us to move toward functional precision oncology — offering patients tailored and more effective treatment options based on their individual disease biology.

III. Molecular Targeting and Clinical Research

Another key focus of our group is to identify new, molecularly targeted therapeutic approaches for AML treatment. One major area of investigation is to study the so-called GLI transcription factors. Here, we were able to develop a novel pharmacological strategy that has shown promising efficacy against AML cells and has already shown encouraging results in first applications in patients. Furthermore, epigenetic factors which contributes to AML progression and maintenance are of special interest. Beside basic research, our high patient volume of approximately 90 newly diagnosed AML cases per year at our department enables us to conduct several clinical and translational projects. These include, for example, real-world data analyses of widely used therapeutics as well as studies addressing infectious complications during therapy.

Research Focus

• Immune phenotyping of different immune cell populations e.g. ab T cells, NK cells, monocytes/macrophages (multiparametric flow cytometry, PCR

• Antibody/nanobody-based immunotherapeutic strategies to re-invigorate effector cells
• Functional evaluation of T cell status (differentiation, proliferation, cytotoxicity) with allogeneic and autologous co-cultures
• Macrophages-mediated ADCP and ADCC
• Primary 2D and 3D cultures

• Molecular profiling and functional evaluation of leukemia-associated genes (CRISPR-Cas9 technique, shRNA-mediated knockdown, overexpression
• Advanced co-culture systems mimicking the bone marrow niche
• In vivo mouse models (syngeneic and xenograft NSGS, NSG)
• Systematically assessment and analyses of large datasets from real-world clinical practice to derive novel insights, verify device safety and performance, treatment outcomes and effectiveness of new treatment strategies and medications

(note: Westendorf was formerly Modemann)

1. Ronnacker J, Muller PJ, Mikesch JH, (…), Modemann F, (…). Gemtuzumab ozogamicin in first-line treatment of CBF-AML: insights from a retrospective multi-center analysis. Leukemia. 2025 Jul 21. doi: 10.1038/s41375-025-02700-9

2. Brauneck E, Leonhardt LG, Assemissen AM, (…), Wellbrock J, (…) Brauneck F. Expression of the TIGIT axis and the CD39/CD73 purinergic pathway in bone metastasis-derived immune cells. Cancer Immunol Immunother. 2025

3. Smit DJ, Pereira-Veiga T, Brauer H, (…), Wellbrock J, (…), Jücker M. Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model. Mol Oncol. 2025 Mar 25. doi: 10.1002/1878-0261.70024

4. Shahswar R, Gabdoulline R, Krueger K, (…), Modemann F, (…). A novel prognostic risk model for patients with refractory/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents. Leukemia. 2025 Jan 8. doi: 10.1038/s41375-024-02501-6

5. Wenderoth L, Asemissen AM, Modemann F, (…). Transferable automatic hematological cell classification: Overcoming data limitations with self-supervised learning. Comput Methods Programs Biomed. 2024 Dec 9;260:108560. doi: 10.1016/j.cmpb.2024.108560

6. Witt M, Oliveira-Ferrer L, Koch-Nolte F, (…), Wellbrock J,Brauneck F. Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction. Oncoimmunology. 2024

7. Krüger J, Wellbrock J, Witt M, (…) Brauneck F. Murine Regulatory CD4+ T Cells Are Increased in Leukemic Spleens and Show High Co-Expression of Co-Regulatory Molecules CD39, CD73, PD1, and TIGIT. Int J Mol Sci. 2024

8. Schoof M, Godbole S, Albert TK, (…), Modemann F,(…). Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures. Nat Commun. 2023 Nov 24;14(1):7717. doi: 10.1038/s41467-023-43564-w

9. Niesen J, Hermans-Borgmeyer I, Krüger C, (…), Modemann F, Schüller U. hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation. iScience 26(9):107501. 2023 July 28. doi: 10.1016/j.isci.2023.107501

10. Brauneck F, Oliveira-Ferrer L, Muschhammer J, (…), Wellbrock J. Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro. Front Immunol. 2023 Oct 2;14:1250258. doi: 10.3389/fimmu.2023.1250258. eCollection 2023.

11. Modemann F, Ahmadi P, von Kroge, (…), Ghandili S. The prognostic impact of lymphoma perforation in patients with primary gastrointestinal lymphoma – a single-center analysis. Leukemia & Lymphoma 2023 Aug 8:1-10. doi: 10.1080/10428194.2023.2240921

12. Bach N, Winzer R, Tolosa E, (…) Brauneck F. The Clinical Significance of CD73 in Cancer. International journal of molecular sciences. 2023

13. Gottschlich A, Thomas M, Grünmeier R, (…), Modemann F, Wellbrock J, (…), Kobold S. Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia. Nat Biotechnol. 2023 Mar 13. doi: 10.1038/s41587-023-01684-0

14. von Kroge PH, Duprée A, Mann O, (…), Modemann F, Ghandili S. Abdominal emergency surgery in patients with hematological malignancies: a restrospective single-center analysis. World J Emerg Surg. 18, 12 (2023). doi.org/10.1186/s13017-023-00481-z. *shared last authorship

15. Brauneck F, Fischer B, Witt M, (…), Ackermann C, Wellbrock J, Haag F, Fiedler W. TIGIT blockade repolarizes AML-associated TIGIT+ M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis. J Immunother Cancer. 2022 Dec;10(12):e004794. doi: 10.1136/jitc-2022-004794.

16. Ghandili S, Lindhauer C, Pischke S, (…), Modemann F. Clinical features of hepatitis E infections in patients with hematological disorders. Haematologica. 2022 Jun 30. doi: 10.3324/haematol.2022.280853.

17. Weimer P, Wellbrock J, Sturmheit T, (...) Brauneck F. Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer. Cells. 2022

18. Klingler F, (…) Brauneck F, (…), Modemann F, Karagiannis P. Retrospective analysis of three induction chemotherapy regimens in acute myeloid leukemia including CPX-351, cytarabine/daunorubicin with and without the addition of cladribine. Leuk Lymphoma. 2022

19. Ghandili S, von Kroge PH, Simon M, (…), Modemann F. Diagnostic Utility of Bronchoalveolar Lavage in Patients with Acute Leukemia under Broad-Spectrum Anti-Infective Treatment. Cancers (Basel). 2022 Jun 2;14(11):2773. doi: 10.3390/cancers14112773

20. Modemann F, Härterich S, Schulze zur Wiesch J, (…), Ghandili S. Efficacy of Tigecycline as Salvage Therapy in Multidrug-Resistant Febrile Neutropenia in Patients with Acute Leukemia—A Single Center Analysis. Antibiotics 2022 Jan 19: 11,128. doi: 10.3390/antibiotics11020128

21. Wildner NH, Walker A, Brauneck F, Ditt V, Peine S, Huber S, Haag F, Beisel C, Timm J, Schulze Zur Wiesch J. Transcriptional Pattern Analysis of Virus-Specific CD8+ T Cells in Hepatitis C Infection: Increased Expression of TOX and Eomesodermin During and After Persistent Antigen Recognition. Front Immunol. 2022 Jun 6;13:886646. doi: 10.3389/fimmu.2022.886646. PMID: 35734162; PMCID: PMC9207347.

22. Brauneck F, Seubert E, Wellbrock J, et al. Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML. Int J Mol Sci. 2021

23. Brauneck F, Weimer P, Schulze zur Wiesch J, (…), Wellbrock J, Fiedler W. Bone Marrow-Resident Vδ1 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma. Front Med. 2021

24. Wellbrock J, Behrmann L, Muschhammer J, Modemann F, (…), Brauneck F, (…). The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia. Ann Hematol. 2021 Dec;100(12):2933-2941. doi: 10.1007/s00277-021-04602-z.

25. Freisleben F, Modemann F, (…), Wellbrock J, Fiedler W. Mebendazole Mediates Proteasomal Degradation of GLI Transcription Factors in Acute Myeloid Leukemia. Int J Mol Sci. 2021 Oct 1;22(19):10670. doi: 10.3390/ijms221910670

26. Modemann F, (…), Ghandili S. COVID-19 and seasonal influenza: a comparative analysis in patients with hematological malignancies. Leukemia & Lymphoma. 2021 Oct 20:1-8. doi: 10.1080/10428194.2021.1992626

27. Brauneck F, Haag F, Woost R, (…), Wellbrock J, (…). Increased frequency of TIGIT CD73-CD8 T cells with a TOX+TCF-1low profile in patients with newly diagnosed and relapsed AML. Oncoimmunology. 2021

28.Teo Hansen Selnø A, Schlichtner S, (…), Wellbrock J, (…). High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells. Front Immunol. 2021 Jun 21;12:675731.

29. Wildner NH, Ahmadi P, Schulte S, Brauneck F, Kohsar M, Lütgehetmann M, Beisel C, Addo MM, Haag F, Schulze Zur Wiesch J. B cell analysis in SARS-CoV-2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID-19. J Leukoc Biol. 2021 Jan;109(1):77-90. doi: 10.1002/JLB.5COVA0620-370RR. Epub 2020 Dec 4. PMID: 33617048; PMCID: PMC10016889.

30. Modemann F, (…), Kröger N. Ruxolitinib plus extracorporeal photopheresis (ECP) for steroid refractory acute graft-versus-host disease of lower GI-tract after allogeneic stem cell transplantation leads to increased regulatory T cell level. Bone Marrow Transplant. 2020 Dec;55(12):2286-2293

31. Velthaus A, Cornils K, Hennigs, (…), Wellbrock J. The Actin Binding Protein Plastin-3 Is Involved in the Pathogenesis of Acute Myeloid Leukemia. Cancers (Basel). 2019 Oct 26;11(11):1663.

32. Stamm H, (…) Brauneck F, (…) Wellbrock J. Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer. Oncoimmunology. 2019 Oct 12;8(12):e1674605. doi: 10.1080/2162402X.2019.1674605. PMID: 31741778; PMCID: PMC6844319.

33. Lange T, Oh-Hohenhorst SJ, Joosse SA, (…), Wellbrock J, (…). Development and Characterization of a Spontaneously Metastatic Patient-Derived Xenograft Model of Human Prostate Cancer. Sci Rep. 2018 Dec 3;8(1).

34. Mussawy H, Viezens L, Schroeder M, (…), Wellbrock J, (…). The bone microenvironment promotes tumor growth and tissue perfusion compared with striated muscle in a preclinical model of prostate cancer in vivo. BMC Cancer. 2018 Oct 16;18(1):979.

35. Sakhnevych SS, Yasinska IM, Bratt AM, (…), Wellbrock J, (…). Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression. Cell Mol Immunol. 2018 Nov;15(11).

36. Yasinska IM, Gonçalves Silva I, Sakhnevych SS, (…), Wellbrock J, (…). High mobility group box 1 (HMGB1) acts as an "alarmin" to promote acute myeloid leukaemia progression. Oncoimmunology. 2018 Feb 27;7(6).

37. Bäder S, Glaubke E, Grüb S, (…), Wellbrock J,(…). Effect of the actin- and calcium-regulating activities of ITPKB on the metastatic potential of lung cancer cells. Biochem J. 2018 Jun 26;475(12).

38. Stamm H, Klingler F, Grossjohann EM, (…), Wellbrock J, Fiedler W. Immune checkpoints PVR and PVRL2 are prognostic markers in AML and their blockade represents a new therapeutic option. Oncogene. 2018 Sep;37(39).

39. Yasinska IM, Ceccone G, Ojea-Jimenez I, (…), Wellbrock J, (…). Highly specific targeting of human acute myeloid leukaemia cells using pharmacologically active nanoconjugates. Nanoscale. 2018 Mar 29;10(13).

40. Heinz LS, Muhs S, Schiewek J, (…), Wellbrock J, (…). Strong fascin expression promotes metastasis independent of its F-actin bundling activity. Oncotarget. 2017 Nov 1;8(66).

41. Täger M, Horn S, Latuske E, (…), Wellbrock J, Jücker M. SHIP1, but not an AML-derived SHIP1 mutant, suppresses myeloid leukemia growth in a xenotransplantation mouse model. Gene Ther. 2017 Nov;24(11).

42. Speidel D, Wellbrock J, Abas M. RUNX1 upregulation by cytotoxic drugs promotes apoptosis. Cancer Res. 2017 Dec 15;77(24).

43. Gonçalves Silva I, Yasinska IM, Sakhnevych SS, (…), Wellbrock J, (…). The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells. EBioMedicine. 2017 Aug;22:44-57.

44. Latuske EM, Stamm H, Klokow M, (…), Wellbrock J. Combined inhibition of GLI and FLT3 signaling leads to effective anti-leukemic effects in human acute myeloid leukemia. Oncotarget. 2017 Apr 25;8(17).

45. Hansen-Algenstaedt N, Kwan MK, Algenstaedt P, (…), Wellbrock J, (…). Comparison between Minimally Invasive Surgery and Conventional Open Surgery for Patients with Spinal Metastasis: A Prospective Propensity Score-Matched Study. Spine (Phila Pa 1976). 2017 May 15;42(10).

46. Schroeder M, Viezens L, Wellbrock J, (…). Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone. J Surg Oncol. 2016 Apr;113(5).

47.Degwert N, Latuske E, Vohwinkel G, (…), Wellbrock J. Deoxycytidine kinase is downregulated under hypoxic conditions and confers resistance against cytarabine in acute myeloid leukaemia.Eur J Haematol. 2015 Nov 27. Eur J Haematol. 2016 Sep;97(3).

48.Wellbrock J, Harbaum L, Stamm H et al. Intrinsic BMP Antagonist Gremlin-1 as a Novel Circulating Marker in Pulmonary Arterial Hypertension. Lung. 2015 Aug;193(4).

49. Wellbrock J, Latuske E, Köhler J, et al. Expression of Hedgehog pathway mediator GLI represents a negative prognostic marker in human acute myeloid leukemia and its inhibition exerts anti-leukemic effects. Clinical Cancer Research 2015;21(10).

50. Kebenko M, Drenckhan A, Gros SJ, (…), Wellbrock J, Fiedler W. ErbB2 signaling activates the Hedgehog pathway via PI3K-Akt in human esophageal adenocarcinoma: identification of novel targets for concerted therapy concepts.Cell Signal, 2015; 27(2).