Tumor immune microenvironment

In our lab, we aim to expand our knowledge of the composition, phenotype, and organization of the tumor immune microenvironment (TiME) in gastrointestinal cancers with the goal to ultimately improve patient care. Our research is located at an exciting interface between basic immunology, translational and clinical research. We use clinical data to guide our research focus, we use systems biology approaches to build hypotheses and then test these hypotheses in functional in vivo and in vitro models. We employ complementary experimental strategies to investigate the TiME in patient samples including scRNA-seq, spatial proteomics and high-dimensional spectral cytometry. Using these approaches, we study how reciprocal communications between the innate and adaptive immune system, stomal cells and cancer cells are altered in response to tumor initiation, progression, and response to (immuno)therapy. One focus of our research program is to investigate the role of tissue-resident lymphocytes, in particular mucosal-associated invariant T (MAIT) cells, in the context of cancer. Beyond that and following up on previous studies, we continue to explore how the liver as a site of primary tumorigenesis or metastasis represents a unique tumor microenvironment that requires special consideration. 

The overarching goal of our research is to translate our findings to the clinic and to develop prudent immunotherapeutic strategies to disrupt the hostile TiME for the benefit of patients with gastrointestinal cancers.

Dr. med. Benjamin Ruf

Dr. med. Benjamin Ruf

Head of the Research group

E-Mail-Adresse: benjamin.ruf@med.uni-tuebingen.de

Publikationen: PubMed

Publikationen: Google Scholar

Personenprofil: Mehr zur Person

Benjamin Ruf is a physician-scientist focusing on tumor immunology and immunotherapy in gastrointestinal cancers. Benjamin received his M.D. from studies at the University of Tübingen, King’s College London and the University of Aberdeen. After graduation, he started residency in Internal Medicine with a focus on Gastroenterology, Hepatology and Gastro-Oncology at the University Hospital in Tübingen, Germany. Between 2019-2023 he did postdoctoral studies at the U.S. National Cancer Institute (NCI). Back in Tübingen, he works as an independent group leader at the M3 Research Institute and the University Hospital Tübingen and tries to better understand how we can use our body’s own immune system to fight cancers.

Overview
Spatially resolved immune cell atlas of human liver cancer generated using the CODEX technology. Left: Six-color overview of a cryosection derived from a human HCC sample, stained with 37 antibodies at the same time. The image shows liver parenchyma with liver sinusoids (LSEC, red), endothelial cells (turquois), hepatocytes (green), biliary epithelial cells (BEC, pink), smooth muscle cells (aSMA+, yellow) and immune cells (white). Middle: higher magnification of the region in the white box. Right: same region as the middle image, but now showing immune cell infiltrates of B cells (red), T cells (turquois), macrophages (Mφ, green) and neutrophils (pink).
Overview
Research strategy in our lab.
TiME
Composition, phenotype, and organization of the tumor immune microenvironment
T (MAIT)
Investigation of the role of tissue-resident lymphocytes
scRNA-seq
Spatial proteomics and high-dimensional spectral cytometry

Selected Publications

  • Ruf, B., Bruhns, M., Babaei, S., Kedei, N., Ma, L., Revsine, M., Benmebarek, M.-R., Ma, C., Heinrich, B., Subramanyam, V., et al. (2023). Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin. Cell 186, 3686-3705.e3632. 10.1016/j.cell.2023.07.026.

  • Ruf, B., Greten, T.F., and Korangy, F. (2023). Innate lymphoid cells and innate-like T cells in cancer - at the crossroads of innate and adaptive immunity. Nat Rev Cancer 23, 351-371. 10.1038/s41568-023-00562-w.

  • Ruf, B., Catania, V. V., Wabitsch, S., Ma, C., Diggs, L. P., Zhang, Q. et al. Activating Mucosal-Associated Invariant T cells Induces a Broad Antitumor Response. Cancer Immunology Research, 2021;9(9):1024-34.

  • Ruf, B., Heinrich, B., and Greten, T.F. (2021). Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells. Cell Mol Immunol 18, 112-127. 10.1038/s41423-020-00572-w.

  • Yang, Y-P., Wistuba-Hamprecht, K, Greten, T.F, Ruf, B., (2024), Innate-like T cells in liver disease. Trends in Immunology. DOI: 10.1016/j.it.2024.05.008.

  • Ma, C., Fu, Q., Diggs, L.P., McVey, J.C., McCallen, J., Wabitsch, S., Ruf, B., Brown, Z., Heinrich, B., Zhang, Q., et al. (2022). Platelets control liver tumor growth through P2Y12-dependent CD40L release in NAFLD. Cancer Cell 40, 986-998 e985. 10.1016/j.ccell.2022.08.004.

  • Zhang Q, Ma C, Duan Y, Heinrich B, Rosato U, Diggs LP, Ruf B, et al. Gut microbiome directs hepatocytes to recruit MDSC and promote cholangiocarcinoma. Cancer Discovery. doi:10.1158/2159-8290.Cd-20-0304 (2020).

  • Heinrich, B., Gertz, E.M., Schaffer, A.A., Craig, A., Ruf, B., Subramanyam, V., McVey, J.C., Diggs, L.P., Heinrich, S., Rosato, U., et al. (2022). The tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma. Gut 71, 1161-1175. 10.1136/gutjnl-2021-325288.

  • Ruf B, Roggia, C., Schroeder, C., Mattern, S., Fend, F., Klag, T., and Gotz, M. (2022). Chromoendoscopy in Combination with Random Biopsies for Patients with Pathogenic CDH1 Mutations Undergoing Endoscopic Surveillance. J Gastrointest Cancer. 10.1007/s12029-022-00831-1.

  • Ruf, B, Berchtold, S., Venturelli, S., Burkard, M., Smirnow, I., Prenzel, T., Henning, S.W., and Lauer, U.M. (2015). Combination of the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus as a new option for epi-virotherapeutic treatment of hepatocellular carcinoma. Mol Ther Oncolytics 2, 15019. 10.1038/mto.2015.19.