Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Guido Kroemer, Paris Descartes University, France
- Second opponent: Clinical Professor Bent Ejlertsen, University of Copenhagen, Denmark
- Third member and chair of the evaluation committee: Researcher Hilde Loge Nilsen, University of Oslo
Chair of the Defence
Professor Ludvig Magne Sollid, University of Oslo
Principal Supervisor
Senior Consultant Jon Amund Kyte, Oslo University Hospital
Summary
Immune checkpoint inhibitors are drugs that block inhibitory immune signals, which may restore anti-tumor immunity and induce durable tumor responses across numerous cancer types. While cytotoxic chemotherapy agents were primarily developed to target rapidly dividing malignant cells, a large body of literature suggests that the immune system plays an integral part in their clinical efficacy. A proposed link between cytotoxic effects and anti-tumor immune responses is the concept of immunogenic cell death (ICD), a stress-induced regulated cell death that triggers the establishment of an adaptive immune response against the dead and dying cells.
In the current thesis, we present results from two randomized clinical phase 2 trials that combine ICD-inducing chemotherapy with immune checkpoint inhibitors (ICI) in metastatic breast cancer.
The ALICE trial showed that the addition of PD-L1 inhibitor atezolizumab to chemotherapy improved progression-free survival in triple-negative breast cancer, irrespective of tumor PD-L1 expression. The combination was safe and tolerable, and patients in the combination arm reported improved quality of life compared to the control arm. ALICE was the first study to suggest benefit from adding ICI to chemotherapy in PD-L1-negative disease and the results were published in Nature Medicine in 2022.
The ICON trial evaluated the addition of ipilimumab and nivolumab to chemotherapy in hormone receptor-positive breast cancer. The study showed that concomitant chemotherapy and ICI led to increased toxicity without improvement of clinical outcome. ICI administered after chemotherapy gave clinical responses in a proportion of patients.
In the third study of the thesis, we show that the analysis of tumor immune gene expression may identify early-stage basal-like breast cancer patients with high anti-tumor immune activity and an excellent prognosis.
These results may contribute to more effective and individualized treatment of breast cancer in the future.
Additional information
Contact the research support staff.