P10

Targeting the intra-metastatic microbiome in colorectal cancer

Project Leaders

Prof. Dr. Bertram Bengsch

University of Freiburg

Dr. Reinhild Feuerstein

University of Freiburg

Research Focus

Nucleolin is important for intracellular transfer of bacteria toward the tumor cell nucleus. Confocal microscopy image of CTC-derived organoids which were co-cultured with GFP-expressing E. coli for 4 hours, in the presence of Cy3-labeled AS1411 aptamer (red) or Cy3-labeled CRO control aptamer (red). Nuclei are labeled with Hoechst33342 (blue).

Identification of specific bacteria in the TME of CRC patients using CyTOF technology. Exemplary composite MIBIscope image shown for CRC patient tissue. Marker expression is visualized by colors as indicated.

Microbial induced signaling in circulation tumor cells (CTCs) primes the pre-metastatic niche in target organs. IP10will explore the molecular mechanisms regulating bacterial uptake at the primary tumor site and their subsequent release in the liver, utilizing murine models of metastatic CRC. Additionally, metastasis-associated microbiomes in human liver metastases across various CMS subtypes will be analyzed. Advanced techniques, including CyTOF and mass cytometry imaging, will elucidate the connections between the metastasis-associated microbiome, microbial-derived signals and metastasis development.

Main Collaborations

Core Team

Prof. Dr. Bertram Bengsch

Project Leader

University of Freiburg

Dr. Reinhild Feuerstein

Project Leader

University of Freiburg

Nele Schauer

Doctoral Researcher
Doctoral Researchers Representative

University of Freiburg

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Publications

Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma

Salié H, Wischer L, D'Alessio A, Godbole I, Suo Y, Otto-Mora P, Beck J, Neumann O, Stenzinger A, Schirmacher P, Fulgenzi CAM, Blaumeiser A, Boerries M, Roehlen N, Schultheiß M, Hofmann M, Thimme R, Pinato DJ, Longerich T, Bengsch B.

Gut. 2025 Feb 6;74(3):451-466. doi: 10.1136/gutjnl-2024-332837. PMID: 39349005

P10

S03

Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver

Luenstedt J, Hoping F, Feuerstein R, Mauerer B, Berlin C, Rapp J, Marx L, Reichardt W, von Elverfeldt D, Ruess DA, Plundrich D, Laessle C, Jud A, Neeff HP, Holzner PA, Fichtner-Feigl S, Kesselring R.

Front Immunol. 2024 Jun 10;15:1388272. doi: 10.3389/fimmu.2024.1388272. eCollection 2024. PMID: 38919609

Single-cell deconvolution reveals high lineage- and location-dependent heterogeneity in mesenchymal multivisceral stage 4 colorectal cancer

Berlin C, Mauerer B, Cauchy P, Luenstedt J, Sankowski R, Marx L, Feuerstein R, Schaefer L, Greten FR, Pesic M, Groß O, Prinz M, Ruehl N, Miketiuk L, Jauch D, Laessle C, Jud A, Biesel EA, Neeff H, Fichtner-Feigl S, Holzner PA, Kesselring R.

Clin Invest. 2023 Dec 28;134(5):e169576. doi: 10.1172/JCI169576. PMID: 38153787

T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma

Barsch M, Salié H, Schlaak AE, Zhang Z, Hess M, Mayer LS, Tauber C, Otto-Mora P, Ohtani T, Nilsson T, Wischer L, Winkler F, Manne S, Rech A, Schmitt-Graeff A, Bronsert P, Hofmann M, Neumann-Haefelin C, Boettler T, Fichtner-Feigl S, van Boemmel F, Berg T, Rimassa L, Di Tommaso L, Saeed A, D'Alessio A, Pinato DJ, Bettinger D, Binder H, John Wherry E, Schultheiss M, Thimme R, Bengsch B.

J Hepatol. 2022 Aug;77(2):397-409. doi: 10.1016/j.jhep.2022.02.032. Epub 2022 Apr 1. PMID: 35367533

P10

P16