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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Diwakar Davar, University of Pittsburgh, USA
- Second opponent: Professor Inge Marie Svane, University of Copenhagen, Denmark
- Third member and chair of the evaluation committee: Professor II Tobias Gedde-Dahl, University of Oslo
Chair of the Defence
Profesor II Pål-Dag Line, University of Oslo
Principal Supervisor
Jon Amund Kyte, Oslo University Hospital
Summary
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but many patients do not respond, and current biomarkers only partly predict treatment benefit. Preclinical, observational, and early clinical studies have linked the gut microbiota to the immune response and to the efficacy of ICIs, suggesting that it may serve both as a therapeutic target and as a biomarker.
This thesis investigated whether fecal microbiota transplantation (FMT) can overcome resistance to ICIs, and whether gut microbiota diversity and composition are associated with outcomes in patients receiving chemotherapy with or without immunotherapy. This was addressed by conducting a phase IIa FMT trial with translational immune and microbiota analyses, and by sequencing fecal samples collected in two randomized breast cancer trials.
In the MITRIC trial, twelve patients with advanced cancer who had progressed on ICIs received repeated FMTs from long-term ICI responders, combined with their prior ICI. FMT plus ICI was safe and feasible, but clinical activity was limited, with no objective responses.
In the ALICE (triple-negative) and ICON (hormone receptor-positive) breast cancer trials, patients received chemotherapy with or without ICIs. High gut microbiota diversity was associated with favorable outcomes in both trials, indicating prognostic value. In ALICE, high diversity was also associated with benefit from adding immunotherapy. Several bacterial taxa associated with clinical benefit were identified.
Overall, this thesis provides insights into the potential role of the gut microbiota as a therapeutic target and biomarker in immuno-oncology. The findings from these articles require validation in future studies, but may help inform further research in this field.
Additional information
Contact the research support staff.