An investigation of the relationship between the systemic inflammatory response, cytokine profile and outcome in patients with renal cancer

Ramsey, Sara (2006) An investigation of the relationship between the systemic inflammatory response, cytokine profile and outcome in patients with renal cancer. MSc(R) thesis, University of Glasgow.

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Abstract

Renal cancer is the 14th most common cancer in the UK, but is the most lethal of urological cancers. 40% of patients present with distant metastases, and 30% of patients undergoing a curative nephrectomy will subsequently develop metastases. For localized disease, the mainstay of treatment is radical nephrectomy. For patients with metastatic disease immunotherapy is the current standard of care, though the median survival is only nine months. In Chapter one, the epidemiology, pathology, clinical presentation and treatment of renal cancer are discussed. In the second chapter we have reported the prognostic value of the cumulative Glasgow Prognostic Score (based on the combination of an elevated C-reactive protein and hypoalbuminaemia) in patients with metastatic renal cancer commencing immunotherapy. The Glasgow Prognostic Score was independently associated with cancer specific survival, in addition to the Memorial-Sloan Kettring Cancer Centre Score, with median survivals of 28, 11 and 3 months for patients with GPS of 0, 1 and 2 respectively. The GPS was also superior in predicting outcomes to another commonly used prognostic score, the Metastatic Renal Cancer Comprehensive Prognostic System. In Chapter three we reported the prognostic significance of C-reactive protein, but not hypoalbuminaemia, in addition to the Leibovich score in UISS low and intermediate risk patients undergoing potentially curative nephrectomy. The presence of an elevated C-reactive protein was independently associated with cancer specific survival in addition to the Leibovich score. Both the Leibovich score and C-reactive protein were superior to the SSIGN score in predicting cancer specific survival. In Chapter four we examined the role of circulating cytokines associated with T-lymphocyte subpopulations in patients with renal cancer. In the presence of a systemic inflammatory response, there was an association with increased cytokine concentrations from both T-helper 1 and T-helper 2 responses. However, cytokine concentrations measured using the Luminex technology were variable, and appeared less reliable than those measured using conventional ELISA technology. In Chapter five, a longitudinal study of cytokine concentrations and circulating T-lymphocytes was performed in patients undergoing immunotherapy for metastatic renal cancer. Analysis of C-reactive protein, circulating T-lymphocytes, circulating cytokines was performed prior to commencement of immunotherapy, and after two to four weeks of treatment. Concentrations of C-reactive protein and interleukin-6 did not alter significantly following instigation of immunotherapy, nor did the numbers of circulating T-lymphocyte subsets. However, there was a significant increase in Interleukin-10 concentrations following commencement of immunotherapy. In Chapter 6, we examined the longitudinal relationship between the systemic inflammatory response, and circulating cytokines in patients undergoing nephrectomy. Both interleukin-6 and interleukin-10 concentrations were elevated in patients with evidence of a systemic inflammatory response. However, on multiple regression analysis only interleukin-6 was significantly correlated with C-reactive protein concentrations. Following nephrectomy, the proportion of patients with an elevated C-reactive protein did not change significantly, nor did concentrations of interleukin-6 normalise. In contrast there was a trend towards significance in the elevation of Interleukin-10 concentrations following nephrectomy. It has been previously suggested that the presence of the systemic inflammatory response in patients with renal cancer is due to secretion of pro-inflammatory cytokines by the tumour itself. It appears clear from the investigations carried out during the course of this thesis that the presence of systemic inflammatory response appears unlikely to be solely be determined by the tumour, but may be as a result of a disordered immune response from the host.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: D C McMillan
Keywords: Immunology, Oncology
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-73729
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56
URI: http://theses.gla.ac.uk/id/eprint/73729

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