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Title: A study to investigate the immune response in ovarian cancer patients treated with chemotherapy
Author: Datta, Shreelata
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Women with ovarian cancer usually present with advanced stage disease and, although sensitive to chemotherapy initially, the majority will relapse following first line treatment. Resistance to chemotherapy contributes to poor prognosis in ovarian cancer. A potential strategy to prolong the response to treatment and reduce chemotherapy resistance is immune based therapies. These therapies are likely to be most effective when disease is minimal or subclinical, such as at completion of first line chemotherapy, but depend on the ability to mobilize a sufficient immune response. Currently, little is known about the immune competence of ovarian cancer patients undergoing chemotherapy or upon its completion. The aim of this study was twofold. By measuring the cellular and humoral immune response to Hepatitis B vaccination we evaluated the immune competence of women once they had completed first-line chemotherapy for ovarian cancer. This provided important information about the optimal time of delivery and likely efficacy of future immune therapeutic strategies, suggesting a significant difference in B cell response between patients treated with chemotherapy and healthy age-matched control patients. A vaccine was used because it essentially replaces an initial infection but still leads to the generation of memory B cells. Secondly, by quantifying peripheral blood mononuclear cell levels of the immune checkpoint inhibitory receptor PD-1 (in lymphocytes) and its ligand, PD-L1 (in monocytes) in ovarian cancer patients undergoing and completing chemotherapy, this study investigated the possibility of using PD-1 and PD-L1 as a biomarker in ovarian cancer treatment. Our results found a significant difference in lymphocytic PD-1 T cell count between patients who had recently completed chemotherapy and those who had completed chemotherapy over a year ago. This suggests further work to characterize lymphocytic PD1 changes after chemotherapy treatment is warranted, to optimize the timing of the delivery of future immunotherapy.
Supervisor: Ghaem-Maghami, Sadaf Sponsor: BMA Foundation ; Vandervall Foundation
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral