Research focus
Our research group investigates the role of the immune system in the development of colorectal cancer and inflammatory bowel diseases.
The intestinal immune system is constantly exposed to various food antigens as well as microbial molecules and metabolites. A healthy gut immunology must balance tolerance to foreign molecules with successful control of invading microbes. Overreaction can lead to inflammatory bowel disease, whereas excessive tolerance can allow malignant cancer cells to develop.
To understand the causes of such dysregulations, we dissect healthy and inflamed intestinal tissue, as well as colorectal cancer and its metastases, and investigate the interplay of immune cells with each other and with other cell types of the intestine, such as epithelial cells, fibroblasts and tumor cells. For this purpose, we perform various phenotypic and functional studies in tissue but also with isolated cells in 3D cultures.
Rudolf Oehler is particularly interested in the role of different forms of cell death (apoptosis, necroptosis, necrosis, etc.) in the immunological events of colon cancer. Tumor growth is always associated with cell death of individual tumor cells and in surrounding tissues. In addition, cancer treatments such as chemotherapy lead to increased cell death. Dying cells release certain molecules that are recognized by cells of the innate immune system such as macrophages or granulocytes. We could show that these cells then release anti-inflammatory molecules that inhibit an immune response against the tumor. Furthermore, also non-professional phagocytes contributes to the clearance of apoptotic cells. Here we are especially interested in the role of fibroblasts.
The goal of the research is to specifically inhibit this escape mechanism of the tumor from the immune system.
Lukas Unger is trying to better understand the exaggerated immune response in chronic inflammatory bowel diseases, especially Crohn's disease. As a visceral surgeon, he is directly involved in the treatment of patients with Crohn's disease. He studies immune system dysregulation in the intestinal mucosa, mesentery, and lymph nodes involved.
Dr. Unger's goal is to develop individualized interventions that can reduce disease recurrence after surgical treatment.
Team
a.o. Univ.Prof. Dr. Rudolf Oehler, PhD
Dr. Lukas UNGER, PhD
Dr. Vasileios GERAKOPOULOS, PhD
Postdoctoral Fellow
Dr. Monika SACHET, PhD
Postdoctoral Fellow
Dr. Sonja KAPPEL-LATIF, PhD
Postdoctoral Fellow
Cristiano RAMOS, MSc
Predoctoral Fellow
Publications
Altered B-Cell Expansion and Maturation in Draining Mesenteric Lymph Nodes of Inflamed Gut in Crohn's Disease Sonja Kappel-Latif, Prasanti Kotagiri, Lukas Schlager, Gabor Schuld, Natalie Walterskirchen, Vanessa Schimek, Gavin Sewell, Carina Binder, Johanna Jobst, Supriya Murthy, Barbara Messner , Stefanie Dabsch, Arthur Kaser, Paul A Lyons, Michael Bergmann, Anton Stift, Rudolf Oehler, Lukas W Unger Cell Mol Gastroenterol Hepatol. 2024;17(4):662-666. doi: 10.1016/j.jcmgh.2023.12.006.Epub 2023 Dec 24.
Differential effects of Epirubicin and Docetaxel on lymphocytes in breast cancer K. Wimmer, S. Frantal, M. Sachet, C. Ramos, H. Birnleitner, C. Brostjan, R. Exner, M. Filipits, Z. Bago-Horvath, M. Rudas, R. Bartsch, M. Gnant, R. Oehler, F. Fitzal,. Journal of Experimental & Clinical Cancer Research. 2023 (in press)
Viability and functionality of human cryopreserved parathyroid tissue (PT): long-term results of a large in vitro study, Hargitai L., Steiner I., Schimek V., Sachet M., Oehler R., Worel N., Scheuba C, Riss P., Niederle B., Current Problems in Surgery. 2023; doi: 10.1016/j.cpsurg.2023.101376
GLP-2 Improves Hepatic Inflammation and Fibrosis in Mdr2-/- Mice Via Activation of NR4a1/Nur77 in Hepatic Stellate Cells and Intestinal FXR Signaling. Fuchs CD, Claudel T, Mlitz V, Riva A, Menz M, Brusilovskaya K, Haller F, Baumgartner M, Königshofer P, Unger LW, Sjöland W, Scharnagl H, Stojakovic T, Busslinger G, Reiberger T, Marschall HU, Trauner M. Cell Mol Gastroenterol Hepatol. 2023;16(5):847-856. doi: 10.1016/j.jcmgh.2023.08.003. Epub 2023 Aug 10.
Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut. Duan J, Matute JD, Unger LW, Hanley T, Schnell A, Lin X, Krupka N, Griebel P, Lambden C, Sit B, Grootjans J, Pyzik M, Sommer F, Kaiser S, Falk-Paulsen M, Grasberger H, Kao JY, Fuhrer T, Li H, Paik D, Lee Y, Refetoff S, Glickman JN, Paton AW, Bry L, Paton JC, Sauer U, Macpherson AJ, Rosenstiel P, Kuchroo VK, Waldor MK, Huh JR, Kaser A, Blumberg RS. Immunity. 2023 May 9;56(5):1115-1131.e9. doi: 10.1016/j.immuni.2023.02.018. Epub 2023 Mar 13.
Evaluation of Intestinal Fibrosis with 68Ga-FAPI PET/MR Enterography in Crohn Disease. Scharitzer M, Macher-Beer A, Mang T, Unger LW, Haug A, Reinisch W, Weber M, Nakuz T, Nics L, Hacker M, Bergmann M, Rasul S. Radiology. 2023 Feb 28:222389. doi: 10.1148/radiol.222389. Online ahead of print.
Circulating caspase-cleaved cytokeratin 18 correlates with tumour burden and response to therapy in patients with colorectal cancer liver metastasis. Singh Bhangu J, Macher-Beer A, Schimek V, Garmroudi B, Tamandl D, Unger LW, Bachleitner-Hofmann T, Oehler R. Clin Chim Acta. 2023 Jan 1;538:53-59. doi: 10.1016/j.cca.2022.11.009. Epub 2022 Nov 11.
Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors, Brandel V., Schimek V., Göber S., Hammond T., Brunnthaler L., Schrottmaier W.C., Mussbacher M., Sachet M., Liang Y.Y., Reipert S., Ortmayr G., Pereyra D., Santol J., Rainer M., Walterskirchen N., Ramos C., Gerakopoulos V., Rainer C., Spittler A., Weiss T., Kain R., Messner B., Gruenberger T., Assinger A., Oehler R., Starlinger P., J. Hepatol. 2022 doi.org/10.1016/J.JHEP.2022.07.027.
Tumour cell apoptosis modulates the colorectal cancer immune microenvironment via interleukin-8-dependent neutrophil recruitment. Schimek V., Strasser K., Beer A., Göber S., Walterskirchen N., Brostjan C., Müller C., Bachleitner-Hofmann T., Bergmann M., Dolznig H., Oehler R. Cell Death & Disease. 2022; 13:113. doi.org/10.1038/s41419-022-04585-3.
Metastatic colorectal carcinoma-associated fibroblasts have immunosuppressive properties related to increased IGFBP2 expression. N. Walterskirchen, C. Müller, C. Ramos, S. Zeindl, S. Stang, D. Herzog, M. Sachet, V. Schimek, L. Unger, V. Gerakopoulos, M. Hengstschläger, T. Bachleitner-Hofmann, M. Bergmann, H. Dolznig, R. Oehler, , Cancer Lett. 540 (2022) 215737. doi.org/10.1016/j.canlet.2022.215737
Chronic CD40L blockade is required for long-term cardiac allograft survival with a clinically relevant CTLA4-Ig dosing regimen. Unger LW, Muckenhuber M, Mahr B, Schwarz C, Pilat N, Granofszky N, Regele H, Wekerle T. Front Immunol. 2022 Dec 8;13:1060576. doi: 10.3389/fimmu.2022.1060576. eCollection 2022.
Multiplexed DNA Methylation Analysis in Colorectal Cancer Using Liquid Biopsy and Its Diagnostic and Predictive Value. Pulverer, W., Kruusmaa, K., Schönthaler, S., Huber, J., Bitenc, M., Bachleitner-Hofmann, T., Bhangu, JS., Oehler, R., Egger, G., Weinhäusel, A. Curr. Issues Mol. Biol. 2021, 43, 1419–1435, doi:10.3390/CIMB43030100.
Stromal fibroblasts shape the myeloid phenotype in normal colon and colorectal cancer and induce CD163 and CCL2 expression in macrophages. Stadler, M.; Pudelko, K.; Biermeier, A.; Walterskirchen, N.; Gaigneaux, A.; Weindorfer, C.; Harrer, N.; Klett, H.; Hengstschläger, M.; Schüler, J.; et al. Cancer Lett. 2021, 520, 184–200, doi:10.1016/j.canlet.2021.07.006.
Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis. Pfisterer N, Unger LW, Reiberger T. World J Hepatol. 2021 Jul 27;13(7):731-746. doi: 10.4254/wjh.v13.i7.731.
Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease. Hartl L, Elias J, Prager G, Reiberger T, Unger LW. World J Gastroenterol. 2021 May 21;27(19):2281-2298. doi: 10.3748/wjg.v27.i19.2281.
Is IL-6 back in trans signalling for inflammatory bowel disease? Unger LW, Kaser A. Gastroenterology. 2021 Mar 19:S0016-5085(21)00539-4. doi: 10.1053/j.gastro.2021.03.030. Online ahead of print.
In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome. Schwarz C, Mahr B, Muckenhuber M, Weijler AM, Unger LW, Pilat N, Latus M, Regele H, Wekerle T. Am J Transplant. 2021 Jun 21. doi: 10.1111/ajt.16724. Online ahead of print.
Distinct roles for major and minor antigen barriers in chimerism-based tolerance under irradiation-free conditions. Mahr B, Pilat N, Granofszky N, Muckenhuber M, Unger LW, Weijler AM, Wiletel M, Steiner R, Dorner L, Regele H, Wekerle T. Am J Transplant. 2021 Mar;21(3):968-977. doi: 10.1111/ajt.16177. Epub 2020 Jul 24.
Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries. GlobalSurg Collaborative and National Institute for Health Research Global Health Research Unit on Global Surgery. Lancet. 2021 Jan 30;397(10272):387-397. doi: 10.1016/S0140-6736(21)00001-5. Epub 2021 Jan 21.
The role of neutrophil death in chronic inflammation and cancer. Brostjan, C.; Oehler, R. Cell Death Discov. 2020. doi: 10.1038/s41420-020-0255-6
Alternative activation of human macrophages enhances tissue factor expression and production of extracellular vesicles. Hohensinner, P.J.; Mayer, J.; Kirchbacher, J.; Kral-Pointner, J.; Thaler, B.; Kaun, C.; Hell, L.; Haider, P.; Mussbacher, M.; Schmid, J.A.; et al. Haematologica 2020, 105, doi:10.3324/HAEMATOL.2019.220210.
Circulating biomarkers of cell death. Wimmer, K.; Sachet, M.; Oehler, R. Clin. Chim. Acta 2020, 500, 87–97. doi: 10.1016/j.cca.2019.10.003
Hepatic Steatosis in Lean Patients: Risk Factors and Impact on Mortality. Unger LW, Forstner B, Muckenhuber M, Scheuba K, Eigenbauer E, Scheiner B, Pfisterer N, Paternostro R, Trauner M, Mandorfer M, Reiberger T. Dig Dis Sci. 2020 Sep;65(9):2712-2718. doi: 10.1007/s10620-019-06000-y. Epub 2019 Dec 24.
Mesenteric granulomas independently predict long-term surgical recurrence risk in Crohn's disease. Unger LW, Argeny S, Stift A, Yang Y, Karall A, Freilinger T, Müller C, Bergmann M, Stift J, Riss S. Colorectal Dis. 2020 Feb;22(2):170-177. doi: 10.1111/codi.14814. Epub 2019 Aug 23.
Global variation in the long-term outcomes of ypT0 rectal cancers. Lorenzon L, Evrard S, Beets G, Gonzalez-Moreno S, Kovacs T, D'Ugo D, Polom K; CORSiCA Study - EYSAC.1 Study Group. Eur J Surg Oncol. 2020 Mar;46(3):420-428. doi: 10.1016/j.ejso.2019.10.010. Epub 2019 Oct 12.
Restoration of intestinal continuity after stoma formation for Crohn's disease in the era of biological therapy : A retrospective cohort study. Müller C, Bergmann M, Stift A, Argeny S, Speake D, Unger L, Riss S. Wien Klin Wochenschr. 2020 Jan;132(1-2):12-18. doi: 10.1007/s00508-019-01586-9. Epub 2020 Jan 8. PMID: 31915925
FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle. Cader MZ, de Almeida Rodrigues RP, West JA, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias-Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A. Cell. 2020 Jan 23;180(2):278-295.e23. doi: 10.1016/j.cell.2019.12.017.
Novel reliability criteria for controlled attenuation parameter assessments for non-invasive evaluation of hepatic steatosis. Georg Semmler, Katharina Wöran, Bernhard Scheiner, Lukas W. Unger, Rafael Paternostro, Judith Stift, Philipp Schwabl, Theresa Bucsics, David Bauer, Benedikt Simbrunner, Albert Friedrich Stättermayer, Matthias Pinter, Michael Trauner, Thomas Reiberger, Mattias Mandorfer. United European Gastroenterology Journal. 2020. https://doi.org/10.1177/2050640619900820
Immunological differences between colorectal cancer and normal mucosa uncover a prognostically relevant immune cell profile. Strasser, K.; Birnleitner, H.; Beer, A.; Pils, D.; Gerner, M.C.; Schmetterer, K.G.; Bachleitner-Hofmann, T.; Stift, A.; Bergmann, M.; Oehler, R. Oncoimmunology 2019, 8, e1537693, doi:10.1080/2162402X.2018.1537693.
Exercise-induced bronchoconstriction, temperature regulation and the role of heat shock proteins in non-asthmatic recreational marathon and half-marathon runners. Bekos C., Zimmermann M., Unger L., Janik S., Mitterbauer A., Koller M.,Fritz R., Gäbler C., Didcock J., Kliman J., Klepetko W., Ankersmit HJ. Sci Rep. 2019 Mar 12;9(1):4168. doi: 10.1038/s41598-019-39983-9.
Controlled attenuation parameter (CAP) does not predict hepatic decompensation in patients with advanced chronic liver disease. Scheiner B, Steininger L, Semmler G, Unger LW, Schwabl P, Bucsics T, Paternostro R, Ferlitsch A, Trauner M, Reiberger T, Mandorfer M. Liver Int. 2019 Jan;39(1):127-135. doi: 10.1111/liv.13943. Epub 2018 Sep 22.
Patterns and prevalence of dyslipidemia in patients with different etiologies of chronic liver disease. Unger LW, Forstner B, Schneglberger S, Muckenhuber M, Eigenbauer E, Scheiner B, Mandorfer M, Trauner M, Reiberger T. Wien Klin Wochenschr. 2019 Sep;131(17-18):395-403. doi: 10.1007/s00508-019-01544-5. Epub 2019 Sep 6.
Guideline-conform statin use reduces overall mortality in patients with compensated liver disease. Unger LW, Forstner B, Schneglberger S, Muckenhuber M, Eigenbauer E, Bauer D, Scheiner B, Mandorfer M, Trauner M, Reiberger T. Sci Rep. 2019 Aug 12;9(1):11674. doi: 10.1038/s41598-019-47943-6.
Portal Hypertension after Liver Transplantation—Causes and Management. Unger LW, Mandorfer M., Reiberger T. Curr Hepatology Rep (2019). https://doi.org/10.1007/s11901-019-00450-8
Outcome of no oral antibiotic prophylaxis and bowel preparation in Crohn's diseases surgery. Unger LW, Riss S., Argeny S., Bergmann M., Bachleitner-Hofmann T., Herbst F., Stift A. Wien Klin Wochenschr. 2019 Mar 6. doi: 10.1007/s00508-019-1475-8. [Epub ahead of print]
Circulating Free Methylated Tumor DNA Markers for Sensitive Assessment of Tumor Burden and Early Response Monitoring in Patients Receiving Systemic Chemotherapy for Colorectal Cancer Liver Metastasis. Bhangu, J.S.; Beer, A.; Mittlböck, M.; Tamandl, D.; Pulverer, W.; Schönthaler, S.; Taghizadeh, H.; Stremitzer, S.; Kaczirek, K.; Gruenberger, T.; et al. Ann. Surg. 2018, 268, 894–902, doi:10.1097/SLA.0000000000002901.
Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis. Wisgrill, L.; Weinhandl, A.; Unterasinger, L.; Amann, G.; Oehler, R.; Metzelder, M.L.; Berger, A.; Benkoe, T.M. J. Pediatr. Surg. 2018. doi: 10.1016/j.jpedsurg.2018.08.003
Effect of pathologist's dedication on lymph node detection rate and postoperative survival in colorectal cancer. Unger LW, Muckenhuber M, Riss S, Argeny S, Stift J, Mesteri I, Stift A. Colorectal Dis. 2018 Apr 28. doi: 10.1111/codi.14241. [Epub ahead of print]. PMID: 29706021
Impaired efferocytosis by monocytes in multiple myeloma. Liang, Y.Y.; Schwarzinger, I.; Simonitsch-Klupp, I.; Agis, H.; Oehler, R. Oncol. Lett. 2018, 16, 409–416, doi:10.3892/ol.2018.8620.
Delta albumin is a better prognostic marker for complications following laparoscopic intestinal resection for Crohn's disease than albumin alone - A retrospective cohort study. Müller C, Stift A, Argeny S, Bergmann M, Gnant M, Marolt S, Unger L, Riss S. PLoS One. 2018 Nov 13;13(11):e0206911. doi: 10.1371/journal.pone.0206911. eCollection 2018.
Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit. 2017 European Society of Coloproctology (ESCP) collaborating group. Colorectal Dis. 2018 Sep;20 Suppl 6:47-57. doi: 10.1111/codi.14373.
Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit. 2017 European Society of Coloproctology (ESCP) collaborating group. Colorectal Dis. 2018 Sep;20 Suppl 6:15-32. doi: 10.1111/codi.14362.
The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit. 2017 and 2015 European Society of Coloproctology (ESCP) collaborating groups. Colorectal Dis. 2018 Sep;20 Suppl 6:69-89. doi: 10.1111/codi.14371.
An international multicentre prospective audit of elective rectal cancer surgery; operative approach versus outcome, including transanal total mesorectal excision (TaTME). 2017 European Society of Coloproctology (ESCP) collaborating group. Colorectal Dis. 2018 Sep;20 Suppl 6:33-46. doi: 10.1111/codi.14376.
Evaluating the incidence of pathological complete response in current international rectal cancer practice: the barriers to widespread safe deferral of surgery. 2017 European Society of Coloproctology (ESCP) collaborating group. Colorectal Dis. 2018 Sep;20 Suppl 6:58-68. doi: 10.1111/codi.14361.
Outcomes after placement of a SX-ELLA esophageal stent for refractory variceal bleeding - a national multicenter study. Pfisterer N, Riedl F, Pachofszky T, Gschwantler M, König K, Schuster B, Mandorfer M, Gessl I, Illiasch C, Fuchs EM, Unger L, Dolak W, Maieron A, Kramer L, Madl C, Trauner M, Reiberger T. Liver Int. 2018 Sep 24. doi: 10.1111/liv.13971. [Epub ahead of print]
Allograft rejection is associated with development of functional IgE specific for donor MHC antigens. Farkas AM, Baranyi U, Böhmig GA, Unger L, Hopf S, Wahrmann M, Regele H, Mahr B, Schwarz C, Hock K, Pilat N, Kristo I, Mraz J, Lupinek C, Thalhamer J, Bond G, Kuessel L, Wlodek E, Martin J, Clatworthy M, Pettigrew G, Valenta R, Wekerle T. J Allergy Clin Immunol. 2018 Aug 9. pii: S0091-6749(18)30997-7. doi: 10.1016/j.jaci.2018.06.034. [Epub ahead of print]
An intra-individual surgical wound comparison shows that octenidine-based hydrogel wound dressing ameliorates scar appearance following abdominoplasty. Matiasek J, Kienzl P, Unger LW, Grill C, Koller R, Turk BR. Int Wound J. 2018 Jun 29. doi: 10.1111/iwj.12944. [Epub ahead of print]
Blockade of adhesion molecule lymphocyte function-associated antigen-1 improves long-term heart allograft survival in mixed chimeras. Pilat N, Sabler P, Klaus C, Mahr B, Unger L, Hock K, Wiletel M, Schwarz C, Kristo I, Regele H, Wekerle T. J Heart Lung Transplant. 2018 Mar 30. pii: S1053-2498(18)31424-4. doi: 10.1016/j.healun.2018.03.016. [Epub ahead of print]
Grants
Österreichische Forschungsförderungsgesellschaft (Vienna)
„Modulation of Myeloid Cells in Colorectal Cancer“
GRANT_NUMBER: 868039
URL: https://projekte.ffg.at/projekt/3067116
Fonds des Bürgermeisters der Bundeshauptstadt Wien
Erwin Schrödinger Fellowship
(07.10.2019 to 06.10.2021)
a.o. Univ.Prof. Dr. Rudolf OEHLER
Forschungslabor Viszeralchirurgierudolf.oehler@meduniwien.ac.at
Tel.: +43 (0)1 40400-73513
Anna Spiegel Center of Translational Research
Lazarettgasse 14
A-1090 Vienna