Samenvatting

Non-small cell lung cancer (NSCLC) occurs in approximately 80-85% of all lung cancer patients and has a 5-year overall survival (OS) of only 15-20%. In this study, 29 NSCLC patients received neoadjuvant treatment with Chemoradiotherapy, Nivolumab, and Ipilimumab. This study aimed to investigate the effects of the treatment on the T cells and NK cells of NSCLC patients. Blood samples were taken at baseline, after finishing Chemoradiotherapy, 0-2 days before surgery, 12 weeks after surgery, and at follow-up time points. Peripheral blood mononuclear cells were isolated from blood by using Ficoll hipaque gradient. Multi-color flow cytometry was used to analyze the T cells and NK cells. A cytometry panel has been created with different lineage, activation, and immune checkpoint markers to define the T cell and NK cell subsets and their activation status.
A decrease in the frequencies of Thelper cells was observed after treatment. Activation of Thelper cells was observed, as the expression of CTLA-4, Ki67, and CD39 increased. Furthermore, the frequencies of
CD8+ T cells increased after treatment and showed an activated status, as the Ki67 and CD39 expression increased. The treatment did not affect the frequencies of the Tregs, but the Tregs were activated after treatment, as increases in CTLA-4 and CD39 expression were observed. Additionally, the treatment did not affect the expression of activation and immune checkpoint markers on NK cells.
However, the frequencies of the NK regulatory cells increased after treatment, whereas NK effector cells decreased.
Thus, frequencies of Thelper cells and NK effector cells decreased, whereas frequencies of CD8+ T cells and NK regulatory cells increased. Furthermore, activation and proliferation were observed in Thelper
cells, CD8+ T cells, and Tregs after treatment. This study may give additional information about the effectiveness of the treatment, with the aim of a higher OS in NSCLC patients.