Mechanisms of immunotherapy resistance in hepatocellular carcinoma

Drake, Thomas M. (2023) Mechanisms of immunotherapy resistance in hepatocellular carcinoma. PhD thesis, University of Glasgow.

Abstract

Hepatocellular Carcinoma is the 7th most common cause of cancer and 2nd highest cause of cancer mortality worldwide. For patients who present with early stage disease, cure can be achieved by surgical resection or liver transplantation. The majority of patients, however, present with late stage disease where palliative therapies are the only treatment option.

Immunotherapy is an emerging and promising treatment option for patients with advanced HCC. It allows a cytotoxic response to be directed against tumours and in some cases, can provide complete and durable disease control. However, not all patients will respond to immune checkpoint inhibition. Evidence suggests this is likely due to tumour intrinsic molecular processes that induce primary or secondary resistance to immunotherapy. Therefore, there is an urgent need to identify new strategies to increase the efficacy of immunotherapy for all patients.

Here, I show the development of genetically engineered mouse models which recapitulate key aspects of the human HCC tumour microenvironment. Using a range of techniques including immunohistochemistry and sequencing, I demonstrate response to immunotherapy in these models is associated with the presence of immune cells and go on to identify potential mechanisms responsible for immunotherapy resistance.

This work will underpin the basis for testing new treatments in relevant model systems, with the overall objective of improving patient care through translation of new therapies which improve responses to immunotherapy.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from Cancer Research UK, The Beatson Cancer Charity, Wellcome Trust, the Royal College of Surgeons of Edinburgh, Tenovus, Iterion therapeutics and Aligos therapeutics.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Bird, Professor Thomas and Sansom, Professor Owen
• Date of Award: 2023
• Depositing User: Theses Team
• Unique ID: glathesis:2023-84000
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 20 Dec 2023 10:57
• Last Modified: 20 Dec 2023 11:38
• Thesis DOI: 10.5525/gla.thesis.84000
• URI: https://theses.gla.ac.uk/id/eprint/84000

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