Microbiome-based Therapies in Cancer Immunotherapy

Our research is dedicated to understanding the crucial role of the human microbiome in cancer and cancer immunotherapy. We focus on the cellular and molecular interactions between the human microbiome, the gastrointestinal mucosa, and the immune system, investigating how microbiota modulates intestinal epithelia and immune cells.

Microbial diversity is a strong predictor of efficacy and toxicity in cancer immunotherapy. Our research is driven by the potential to enhance cancer immunotherapy by exploring how bacteria modulate this effect and uncovering the molecular mechanisms underlying them. We are particularly interested in microbial products that protect the intestinal epithelium, potentially mitigating toxicities in cancer immunotherapy and others that can boost anti-tumor immune responses and enhance immunotherapy.

Our research, as part of the collaborative research center 1371, a DFG-funded consortium, aims to develop microbiome-based therapies by combining clinical expertise in hematological malignancies and immunotherapies with the rigorous collection of human bio-samples, matching clinical data and integration into cutting-edge analytical pipelines. Microbiome-based therapies have the potential to significantly improve clinical outcomes in patients receiving immunotherapy.

Dr. med. Alix Schwarz
Clinician scientist

Sandra Rast, M.Sc.
Lab manager

cand. med. Sofia Göldel
Medical student

cand. med. Mats Urban
Medical student

• Innovative Research Projects: We undertake research projects that explore novel concepts and develop cutting-edge technologies related to the microbiome and cancer immunotherapy.
• Collaborations: We forge strategic partnerships with leading institutions, industry partners, and research organizations, amplifying the scope and impact of our work.
• Mentorship and Training: We are deeply committed to the professional development of our members, offering a comprehensive array of training in research methodologies, scientific writing, and presentation skills, coupled with career development guidance, to ensure their future success in academia or industry.
• Outreach and Engagement: We participate in outreach activities, including workshops, seminars, and public lectures, to engage with the broader community and promote interest in the field.

• Thiele Orberg E, Meedt E, Hiergeist A, Jinling X, Heinrich P, Ghimire S, Miltiadous O, Lindner S, Tiefgraber M, Göldel S, Eismann T, Schwarz A, Göttert S, Jarosch S, Steiger K, Schulz C, Gigl M, Fischer J, Janssen KP, Quante M, Heidegger S, Herhaus P, Verbeek M, Ruland J, van den Brink RM, Weber D, Edinger M, Wolff D, Busch D, Kleigrewe K, Herr Wolfgang, Bassermann F, Gessner A, Deng Li, Holler E, Poeck H.
  Bacteria and Bacteriophage Consortia are Associated with Protective Intestinal Metabolites in Patients Receiving Stem Cell Transplantation
  • Nature Cancer 2024
  • doi: 10.1038/s43018-023-00669-x
• Czech M, Schneider S, Peltokangas N, El Khawanky N, Ghimire S, Andrieux G, Hülsdünker J, Krausz M, Proietti M, Haring E, Braun L, Pfeifer D, Schmitt-Graeff A, Grimbacher B, Aumann K, Kircher B, Tilg H, Raffatellu M, Thiele Orberg E, Häcker G, Duyster J, Köhler N, Holler E, Nachbaur D, Boerries M, Gerner R, Grün D, Zeiser R
  Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease.
  • Sci. Transl. Med. 2024
  • doi: 10.1126/scitranslmed.adi1501
• Joachim L, Göttert S, Sax A, Steiger K, Neuhaus K, Heinrich P, Fan K, Thiele Orberg E, Kleigrewe K, Ruland J, Bassermann F, Herr W, Posch C, Heidegger S, Poeck H.
  The microbial metabolite desaminotyrosine enhances T-cell priming and cancer immunotherapy with immune checkpoint inhibitors.
  • EBioMedicine 2023
  • doi: 10.1016/j.ebiom.2023.104834
• Jarosch S, Köhlen J, Ghimire S, Thiele Orberg E, Hammel M, Gaag D, Evert M, Janssen KP, Hiergeist A, Gessner A, Weber D, Meedt E, Poeck H, D'Ippolito E, Holler E, Busch DH.
  Multimodal immune cell phenotyping in gastrointestinal biopsies reveals microbiome-related T cell modulations in human GvHD
  • Cell Reports Medicine 2023
  • doi: 10.1016/j.xcrm.2023.101125
• Wahida A, Müller M, Hiergeist A, Popper B, Steiger K, Branca C, Tschurtschenthaler M, Engleitner T, Donakonda S, De Coninck J, Öllinger R, Pfautsch MK, Müller N, Silva M, Usluer S, Thiele Orberg E, Böttcher JP, Pfarr N, Anton M, Slotta-Huspenina JB, Nerlich AG, Madl T, Basic M, Bleich A, Berx G, Ruland J, Knolle PA, Rad R, Adolph TE, Vandenabeele P, Kanegane H, Gessner A, Jost PJ, Yabal M.
  XIAP restrains TNF-driven intestinal inflammation and dysbiosis by promoting innate immune responses of Paneth and dendritic cells.
  • Science Immunology 2021
  • doi: 10.1126/sciimmunol.abf7235
• Fischer JC, Bscheider M, Göttert S, Thiele Orberg E, Combs SE, Bassermann F, Heidegger S, Haas T, Poeck H.
  Type I interferon signaling before hematopoietic stem cell transplantation lowers donor T cell activation via reduced allogenicity of recipient cells.
  • Scientific Reports 2019
  • doi: 10.1038/s41598-019-51431-2
• Chung L & Thiele Orberg E, Geis AL*, Chan J, Fu K, DeStefano Shields C, Dejea C, Fathi P, Chen J, Finard B, Tam A, McAllister F, Fan H, Wu X, Ganguly S, Lebid A, Metz P, Van Meerbeke S, Huso DL, Wick E, Pardoll DM, Wan F, Sears CL, Housseau F.
  Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells.
  • Cell Host & Microbe 2018
  • doi: 10.1016/j.chom.2018.01.007
• Thiele Orberg E, Fan H, Tam A, Wu S, Wu X, Ganguly S, Fu J, Pardoll DM, Sears CL, Housseau F.
  The myeloid immune signature of Enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.
  • Mucosal Immunology 2017
  • doi: 10.1038/mi.2016.53

Further publications can be found on Pubmed.

• Arbeitsgruppe Poeck "Gezielte Immunmodulation in Krebs”
• Arbeitsgruppe Meedt/Weber/Holler "Translationale GVHD Forschung”
• Arbeitsgruppe Wolff "cGvHD - NIH Consensus Projekt Immunmonitoring und Biomarker der cGvHD”
• Arbeitsgruppe Hansmann "Experimentelle Tumorimmunologie"
• Institut für Mikrobiologie und Hygiene (Prof. André Gessner, Dr. Andreas Hiergeist)
• DFG Sonderforschungsbereich 1371 “Mikrobiom Signaturen”

For more information about our research and publications or to inquire about collaboration opportunities, please get in touch with us at erik.orberg@ukr.de. We look forward to connecting with you!