Role of natural killer cells in cancer and autoimmune diseasescolorectal cancer and rheumatoid arthritis as models /

Linked Agent
Maghazachi, Azzam, Thesis advisor
Date Issued
2020
Language
English
Thesis Type
Dissertations
Abstract
Natural killer (NK) cells have been described to play a critical role in cancer and autoimmune diseases. However, these cells face multiple obstacles in performing their cytolytic functions, such as inability to migrate towards cancer sites. Besides, the role of NK cells in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) has not been clearly identified. Hence, this study aimed at increasing NK cell migration to colorectal cancer sitesusing dimethyl fumarate (DMF) or monomethyl fumarate (MMF)as well asinvestigating potential NK cell markers that may aid in understandingthe state of NK cells in RA.Recombinant chemokines and supernatants collected from the cell line HCT-116 were used in chemotaxis and calcium mobilization of NK92 cell line. Upon pretreatment of NK92 with DMF or MMF, flow cytometry, western blot, qPCR and cytotoxicity assays were performed. In order to assess the role of NK cells in RA, insilicotools were used to identify genes that differentiate between various immune cells and NK cells, as well as NK cells of RA patients and healthy controls. This was validated on freshly isolated peripheral blood mononuclear cells and NK cellsofhealthy and RA individuals. CCL27, CCL28,CXCL16, and HCT-116 supernatants induced chemotaxis and mobilization of intracellular calcium in NK92 cells. Additionally, MMF or DMF pretreatment of NK92 cells upregulated the receptors CCR10 and CXCR6 and increased NK cytolytic activity. Besides, the identified genes were validated to be differentially expressed in NK cells compared to PBMCs as well as between NK cells of RA patients and healthy controls. In conclusion, this study aids in further understanding the potential role of NK cells in cancer andautoimmune diseases.Hence, our results suggest that NK cells could be harnessed as a tool for cancer immunotherapy and RA diagnosis.
Note
A thesis submitted in partial fulfillment of the requirements for the Ph.D. in Molecular Medicine and Translational Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates;Copyright 2020 [Noha Mousaad Elemam]
Category
Disseration
Library of Congress Classification
QW568 .EM53r 2020
Local Identifier
b12873718