{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/322754"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/322754","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Imaging Biomarkers of Response to Immune Checkpoint Inhibition in Melanoma","abstract":"Immune checkpoint inhibition using monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death receptor-1 (PD-1) to enhance cytotoxic T-lymphocyte response against tumours has been used in the management of several malignancies including metastatic melanoma. Although preliminary studies in patients with untreated metastatic melanoma demonstrated significantly increased progression-free survival, there is an unmet need for clinical decision-making tools that can be used for monitoring the efficacy of these costly agents, their potential side effects and the identification of patients with the most suitable immunological profile for this treatment approach. The development of non-invasive imaging methods and imaging biomarkers of response to immune checkpoint inhibitors could therefore provide important diagnostic and prognostic information. This project builds on existing technologies in Cambridge to develop structural and functional imaging approaches for monitoring tumour response to immune checkpoint inhibitors. Magnetic resonance imaging (MRI), radiolabelling of neutrophils for single-photon emission computed tomography (SPECT) imaging and intravital imaging are explored as part of a co-clinical study on metastatic melanoma patients and syngeneic mouse models of cancer immunotherapy.","abstract_html":"Immune checkpoint inhibition using monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death receptor-1 (PD-1) to enhance cytotoxic T-lymphocyte response against tumours has been used in the management of several malignancies including metastatic melanoma. Although preliminary studies in patients with untreated metastatic melanoma demonstrated significantly increased progression-free survival, there is an unmet need for clinical decision-making tools that can be used for monitoring the efficacy of these costly agents, their potential side effects and the identification of patients with the most suitable immunological profile for this treatment approach. The development of non-invasive imaging methods and imaging biomarkers of response to immune checkpoint inhibitors could therefore provide important diagnostic and prognostic information. This project builds on existing technologies in Cambridge to develop structural and functional imaging approaches for monitoring tumour response to immune checkpoint inhibitors. Magnetic resonance imaging (MRI), radiolabelling of neutrophils for single-photon emission computed tomography (SPECT) imaging and intravital imaging are explored as part of a co-clinical study on metastatic melanoma patients and syngeneic mouse models of cancer immunotherapy.","abstract_has_math":false,"creators":["Lau, Ai Hui Doreen"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Gallagher, Ferdia Aidan"],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-09-29","date_published":"2020-09-29","updated_at":"2026-07-22T22:24:13Z","subjects":["Immune checkpoint","CTLA-4","PD-1","MRI","SPECT","intravital imaging","melanoma"],"languages":["eng"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/07aeca62-e868-4863-95cc-ec5e0bca7204/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000276232401"],"render_values":[{"text":"0000-0002-7623-2401","href":"https://orcid.org/0000-0002-7623-2401","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.70210","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gallagher, Ferdia Aidan"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["This project received generous support from the CRUK Cambridge Centre (C9685) and Cambridge Commonwealth, European and International Trust PhD Scholarship to Doreen Lau, Cancer Research UK (CRUK; C19212/A16628, C19212/A911376), the CRUK & Engineering and Physical Sciences Research Council (EPSRC) Cancer Imaging Centre in Cambridge and Manchester (C197/A16465) to Prof. Ferdia Gallagher, CRUK Cambridge Centre Imaging Theme Project Grant (CCCIT-09) to both Doreen Lau and Prof. Ferdia Gallagher and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre."]},{"key":"dc:creator","label":"Author","values":["Lau, Ai Hui Doreen"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000276232401"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2020-09-29"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/322754"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immune checkpoint","CTLA-4","PD-1","MRI","SPECT","intravital imaging","melanoma"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/07aeca62-e868-4863-95cc-ec5e0bca7204/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.70210"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c31f431c-812f-4024-a4e3-9cf31ddc7970/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Immune checkpoint inhibition using monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death receptor-1 (PD-1) to enhance cytotoxic T-lymphocyte response against tumours has been used in the management of several malignancies including metastatic melanoma. 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