Trial Lecture – time and place
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Adjudication committee
- First opponent: Associate Professor Marco Willem Schilham, Department of Pediatrics, Leiden University Medical Centre, The Netherlands
- Second opponent: Professor Martha Chekenya Enger, The Department of Biomedicine, University of Bergen
- Third member and chair of the evaluation committee: Professor Tore Jahnsen, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Michael Daws, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor Marit Inngjerdingen, Faculty of Medicine, University of Oslo
Summary
Cancer in children is rare, yet one of the leading causes of death in school children in Europe. In children, acute leukemia is the most common cancer, and mainly represented by acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Treatment of acute leukemia has been immensely successful in improving survival rates over the last four decades. However, the survival curves have plateaued, and more intensified chemotherapy is not an option, as it increases the risk of both short- and long-term toxicities.
NK cells represent the third largest population of lymphocytes, and are known for their ability to recognize and kill virally infected cells and cancer cells. The aim of the thesis was to characterize the NK cells present in pediatric patients with acute leukemia in order to understand how NK cells are affected by leukemia. Mechanistic studies in a human model is challenging. Therefore, a rat model allowed us to directly study the interaction between NK cells and leukemic cells, as well as the effect of cytokine pre-activated NK cell in therapy for acute leukemia that might be translated to treatment of human T-ALL.
In humans and rats, we observed altered NK cell immunophenotypes, impaired NK cell maturation and reduced effector functions. Our analyses showed that NK cells have a general suppressed phenotype with high levels of certain inhibitory receptors in all patient groups, and that having acute leukemia is more determining for the changes at large, with little differences between T-ALL, BCP-ALL and AML. Leukemia cells have developed strategies to escape NK cell immunosurveillance, and we showed that rat T-ALL blasts are poorly targeted by NK cells. However, this resistance was overcome by targeting the leukemia with cytokine pre-activated NK cells, and this could represent a valuable strategy to treat leukemia.
Additional information
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