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Adjudication committee
- First opponent: Professor Sine Reker Hadrup, Technical University of Denmark, Copenhagen
- Second opponent: Chief Physician Tarje Halvorsen, St Olavs Hospital, Trondheim
- Third member and chair of the evaluation committee: Associate Professor Tor Erik Rusten, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor Øyvind Bruland, Institute of Clinical Medicine, University of Oslo
Principal Supervisor
Professor II Åslaug Helland, Institute of Clinical Medicine, University of Oslo
Summary
Lung cancer is a disease with poor prognosis, especially when diagnosed at an advanced stage. Immunotherapy has improved long-term survival for patients with metastatic non-small cell lung cancer. However, most patients do not experience lasting effect of this treatment.
The aims of the thesis were to investigate how the host’s immune response against tumor affects prognosis in patients with non-small cell lung cancer, and to explore how therapy can support the immune system in eliminating malignant cells when these have managed to escape immune surveillance.
Prognostic factors were investigated in 78 patients with advanced non-small cell lung cancer receiving immune checkpoint blockade. Signs of systemic inflammation, as high CRP and high neutrophil / lymphocyte ratio, were associated with poor short-term prognosis. Radiotherapy prior to immunotherapy was associated with better prognosis after the first 6 months of follow-up.
Combined radiotherapy and immunotherapy was further investigated in a clinical trial. Dynamics in the T cell repertoire in blood was followed in 15 patients over time. Most patients with a response had T cell clones that expanded after treatment initiation. This was reversed at progression. There were also new T cell clones detected after treatment. This may indicate that new antigens were exposed to the immune system when cancer cells were damaged by radiotherapy, mimicking the effect of a cancer vaccine.
Lastly, immune cell infiltration was investigated in almost 400 surgically treated non-small cell lung cancer tumors. The strength and kind of immune response varied greatly between tumors. As immune checkpoint inhibitors act by releasing the break on the anti-tumor immune response, it seems plausible that those with tumors with high immune infiltration and high expression of immune checkpoint proteins would benefit most from immunotherapy as a supplement to standard treatments.
Additional information
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