Circulating tumor cells (CTC) have potential for diagnosis, monitoring of therapy response and evaluation of disease evolution. In this thesis we evaluated possible clinical applications of CTC. CTC compared well with other options for ‘liquid biopsies’. CTC could be used to identify patients who had a lower chance to respond to therapy, independent of the treatment group. Unfortunately clinical application remain limited because the low number of CTC that are detected in the blood. Apheresis is a possible solution, as it allows for the screening of a larger volume of blood. In the apheresis product there seem to be sufficient CTC for use clinically, but we are not yet technologically capable of processing the whole product.
To better understand how CTC are released in the bloodstream we measured CTC in a peripheral vein and a vessel close to the tumor. During surgery a large amount of epithelial cells (majority without genomic aberrations) were released into the bloodstream. Only a minority was identified in the peripheral vein, indicating a central clearance.
Subtypes of lung cancer differed consistently in only a small number of genes, but changes in immune related genes were similar. Especially the antigen presenting genes had a different expression compared to normal tissue and this could be a main method of immune evasion.
The composition of the immune infiltrate is also of importance. Smoking seems to influence the immune infiltrate, increasing the cell fractions that are associated with worse survival.