@masterthesis{Jayalath, type = {Bachelor Thesis}, author = {Jayalath, Pramudini Saubhagya}, title = {Similarities Between Pathogenic CD4+ T Cells in PD-1 Immune Checkpoint Inhibitor Induced Arthritis and Rheumatoid Arthritis}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1383-opus4-10981}, school = {Hochschule Rhein-Waal}, pages = {52}, abstract = {Immune checkpoint inhibitors (ICI) such as anti-CTLA-4 or anti-PD-1 are an efficient and standard treatment option for cancer patients today. However, the treatment with immune checkpoint inhibitors often leads to immune-related adverse events, including Rheumatoid arthritis. Despite the use of ICI for cancer patients dates back to a couple of years, by this time, there are many cases described about RA occurring after ICI treatment. In most cases, the appearance of RA has occurred after anti-PD-1 treatment. Nevertheless, the cause of the induced RA after ICI treatment is poorly understood and poorly investigated. We investigated the cytokine expression of CD4+ T cells isolated from an anti-PD-1 treated cancer patient and analysed the different subpopulations of CD4+ T cells, such as Th1 and Th17 cells. Due to the limited availability of blood samples from ICI treated cancer patients with RA from the University Hospital of Cologne, blood samples were also analysed from RA patients. In this case, the isolated CD4+ T cells were treated in vitro with or without anti-PD1 antibody. By flow cytometry analysis, Th1, Th17 and Treg cell populations of the different groups were determined. In vitro PD-1 treatment has shown a distinct effect after 48 hours on the CD4+ T cells from RA patients. Treatment with anti- PD-1 inhibited the cytokine expression of IFNγ and IL-17 of the CD4+ cells isolated from RA patients; therefore, fewer cells were differentiated into Th17 cells. The same effect was observed on CD4+ T cells from healthy individuals. The differentiation into regulatory T cells was also concerned by PD-1 treatment. There were fewer Treg cells detected from the group of RA patients but not in the group of healthy individuals. The result suggests that CD4+ T cells from RA patients show more resistance to PD1 mediated regulation than CD4+ T cells from healthy individuals or cancer patients. Our findings shed insight into the effect of anti-PD-1 treatment on CD4+ T cells. However, more research is needed to clarify the background of ICI induced RA in cancer patients. Furthermore, ICI therapy is becoming a standard treatment for multiple cancer types. Thus it is important to make awareness of the potential irAEs of immunotherapy among cancer patients.}, language = {en} }