Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: Anti-PD1 therapy has shown great promise in the treatment of cancer patients by blocking the inhibitory immune checkpoint molecule, programmed cell death protein 1 (PD1), thus allowing cytotoxic T-cells to regain their potential to attack cancer cells.However, the effects of anti-PD1 treatment on other cytotoxic cells like NK-cells has not yet been described.Therefore, the aim of this study was to discover the effects of anti-PD1 therapy on NK-cells in melano ma patients treated with nivolumab or pembrolizumab.Peripheral blood samples were obtained from melanoma patients (n = 14) at three different time points; pretreatment, post infusion, and 1 month after the initiation of treatment.The immunophenotype and function of NK-cells were analyzed at each time point.The immunophenotype of NK-cells was determined by flow cytometry and the function of patient NK-cells was studied in real-time cell impedance based cytotoxicity assay and RNA expression analysis by qRT-PCR.Before initiation of treatment, the cytokine producing population of NK-cells presented an activated phenotype in a proportion of melanoma patients and the expression of cytotoxic genes was downregulated when compared to healthy controls.However, after the start of anti-PD1 therapy NK-cells regained their cytotoxic potential in a proportion of patients due to the increased expression of cytotoxic ity genes and enhanced cytotoxic activity in real-time killing assay, thus potentially enhancing the antitumor immunity in these patients.Based on these results, we conclude that anti-PD1 treatment improves the function of NK-cells in a proportion of melanoma patients.
Author: Henna Hakanen
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Itä-Suomen Yliopisto
OpenAlex ID: W3096182930