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Title: A study of the influence of cytokine andchemokine expression on thepathogenesis and clinical behaviour ofEBV-associated Hodgkin's lymphoma
Author: Reynolds, Gary Michael
ISNI:       0000 0004 2670 1876
Awarding Body: University of Wolverhampton
Current Institution: University of Wolverhampton
Date of Award: 2008
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Cytokines and chemokines control the fine balance of immunity and inflammation within the body. Some tumours are capable of utilising these, to promote their own growth and survival. This is particularly apparent in Hodgkin's lymphoma (HL) where the malignant Hodgkin Reed-Sternberg (HRS) cells comprise 1% of the total cellular infiltrate. The rest of the infiltrating mass resembles chronic inflammation, probably under the influence of cytokines and chemokines produced by the HRS cell. A proportion of the HL cases are associated with the Epstein-Barr virus (EBV). EBV can de-regulate cytokine and chemokine expression and might therefore contribute to the immune infiltrate. In this study a modified antigen retrieval method was developed to enable the investigation of expression of cytokines and chemokines by immunohistochemistry. This method was used to show that interleukin-6 (lL-6) expression by HRS cells is associated with the presence of 'B' symptoms and with an increased likelihood of failure to achieve complete remission in patients with advanced HL. The same approach was used to demonstrate that Fractalkine (FKN) is expressed by the majority of HRS cells. An association between FKN expression and increased frequency ofGranzyme B+ (GrB) cytotoxic T-cells (CTLs) was also seen. Affymetrix gene profiling was used to identify cytokines and chemokines whose expression was influenced by EBV infection of HL cell lines. This analysis showed that CXCR4 and CCL20 were up-regulated by EBV infection; immunohistochemistry on HL cases showed a similar association. EBV+/CXCR4+ cell lines were shown to be capable of migrating towards a CXCLl2 gradient. Transwell assays using conditioned media from EBV+ICCL20+ cell lines, showed a chemotaxic effect on a population of peripheral blood mononuclear cells (PBMC) which was three fold greater than media from EBV-ICCL20-. In conclusion, this study has gathered more important information concerning the role of cytokines and chemokines in HL, this may also assist in identifying targets for future therapeutic treatments of the disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available