Research

Cancer is one of the most common causes of death worldwide. More than 90 percent of all cancers are not caused by germline mutations, but rather by acquired somatic mutations and environmental factors. Intriguingly, the microbiota has recently emerged as one such environmental factor, shedding light on previously unexpected mechanistic connections between microbial colonization and neoplastic transformation.

We are studying the cross-talk between cancer cells, immune cells, microbial colonization, metabolism and other environmental or clinical factors. We hope that discovering new connections between these players involved in tumorigenesis might lead to the development of new therapeutic approaches.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and screening and improved early detection methods are key in preventing CRC. This project focusses on the role of the microbiota in the development and progression of CRC, and is aimed at novel therapeutic biomarker discovery for better CRC diagnosis and prediction of anti-CRC therapy efficacy. We explore differences the microbiome, including compositional diversity parameters and abundance of specific bacterial taxa, between healthy humans who underwent routine colonoscopy and patients diagnosed with colorectal adenomas or carcinomas. Additionally, we are interested in the association of the microbiota with anti-cancer therapy efficacy and outcomes in longitudinally-followed CRC patients. We employ orthotopic cancer mouse models to investigate the role of specific bacterial strains on tumour growth and to study bacterial translocation to the tumour microenvironment.

Pancreatic cancer (PC) is among the top four leading causes of cancer-related deaths worldwide, with a five-year survival rate of just 8%. Patient outlook could be drastically improved if PC is detected earlier, for which better diagnostic biomarkers are currently needed. Recently, the intestinal and intra-pancreatic microbiome has been linked to the risk for development of PC, chemotherapy efficacy and toxicity, and long-term survival of PC patients. We investigate the role of the microbiome in PC, specifically aiming at the discovery of prognostic microbial biomarkers for post-operative morbidity and tumour recurrence. We are also interested in the association of the microbiota with chemotherapy response and chemotherapy-associated side effects in pancreatic and hepatobiliary cancer patients. We empoy mouse models to study the effect of microbiota manipulations and specific bacterial strains on orthotopic tumour progression.

Immunotherapy leverages the capacity of the body's own immune system to fight cancer and it comprises several novel and promising therapies, such as Chimeric Antigen Receptor (CAR) T cell therapy, for different types of hard-to-treat blood cancers. Several clinical studies on CD19-targeting CAR-T therapies to treat patients with hematologic malignancies have shown potent anti-tumour efficacy and impressive initial remission rates. However, long-term remission is only achieved in a subgroup of patients and CAR-T therapy is associated with severe and potentially lethal adverse effects, including cytokine release syndrome (CRS) and neurotoxicity (ICANS). Recently, the human gut microbiota was linked to the efficacy and toxicity of immunotherapies such as immune checkpoint inhibition and allogeneic hematopoietic cell transplantation. We hypothesize that the composition of the intestinal microbiota sampled in patients before CAR-T cell infusion and throughout the course of the stay in the hospital is associated with anti-tumour efficacy and adverse toxic side-effects. Additionally, we investigate the pathophysiological relevance of the intestinal microbiota on CAR-T treatment outcomes in mouse models in order to understand the biology of the microbiota on T-cell immunotherapy

University Clinic Heidelberg (Schmitt / Dräger, department IV)
NCT (Jäger, Halama, medical oncology)
LMU (Subklewe, III. Med; Illmer, Chirurg. Klinik)
TUM (Saur, DKT; Poeck, III. Med)
University Regensburg (Abken, RCII; Holler, III. Med)
MSKCC (Van den Brink)
U Chicago (Pamer)