{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/366969"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/366969","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Using Tumour Evolution to Understand the Epigenetic and Transcriptional Adaptations of Cancer to Host Immunity","abstract":"Immunoediting describes the process in tumour development whereby tumours evolve to avoid the immune system. The relevance of immunoediting in carcinogenesis, metastasis and immunotherapy resistance makes understanding the mechanisms of immunoediting essential in informing cancer therapy and prevention. Previous work on immunoediting has largely focussed on neoantigen loss, but this thesis aimed to expand the immunoediting paradigm to incorporate transcriptomic and epigenetic changes in tumour cells. This thesis describes the epigenetic and transcriptomic characterisation of carcinogen-induced immunoedited and unedited tumour lines after growth *in vitro*. The transcriptome and immune infiltrate of immunoedited tumours undergoing progressive growth, or unedited tumours undergoing immune-mediated regression in wild-type mice was investigated. The results suggested that expression of T cell inhibitory molecules, a reduction in inflammation, and reduced expression of L1 transposable elements may be involved in immune escape in immunoedited tumours. An over-expression screen was performed to attempt to identify key genes involved in immunoedited tumour escape *in vivo*. Finally, a collection of bioinformatic tools were developed to perform process-based analysis of The Cancer Genome Atlas. These tools can suggest hypotheses of gene function and regulatory mechanisms and explore the pathological significance of gene expression signatures in human cancers. These tools are publicly available as an online web-tool. Both the identification of potential mechanisms of immunoediting and the bioinformatics tools developed in this thesis can support and inform further research.","abstract_html":"Immunoediting describes the process in tumour development whereby tumours evolve to avoid the immune system. The relevance of immunoediting in carcinogenesis, metastasis and immunotherapy resistance makes understanding the mechanisms of immunoediting essential in informing cancer therapy and prevention. Previous work on immunoediting has largely focussed on neoantigen loss, but this thesis aimed to expand the immunoediting paradigm to incorporate transcriptomic and epigenetic changes in tumour cells. This thesis describes the epigenetic and transcriptomic characterisation of carcinogen-induced immunoedited and unedited tumour lines after growth *in vitro*. The transcriptome and immune infiltrate of immunoedited tumours undergoing progressive growth, or unedited tumours undergoing immune-mediated regression in wild-type mice was investigated. The results suggested that expression of T cell inhibitory molecules, a reduction in inflammation, and reduced expression of L1 transposable elements may be involved in immune escape in immunoedited tumours. An over-expression screen was performed to attempt to identify key genes involved in immunoedited tumour escape *in vivo*. Finally, a collection of bioinformatic tools were developed to perform process-based analysis of The Cancer Genome Atlas. These tools can suggest hypotheses of gene function and regulatory mechanisms and explore the pathological significance of gene expression signatures in human cancers. These tools are publicly available as an online web-tool. Both the identification of potential mechanisms of immunoediting and the bioinformatics tools developed in this thesis can support and inform further research.","abstract_has_math":false,"creators":["Baird, Tarrion"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Roychoudhuri, Rahul"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-11-24","date_published":"2023-11-24","updated_at":"2026-07-22T22:24:07Z","subjects":["immunoediting"],"languages":["eng"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/37ce1be9-9382-4436-9c16-958d9ad4dcdd/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.107681","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Roychoudhuri, Rahul"]},{"key":"dc:creator","label":"Author","values":["Baird, Tarrion"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2023-11-24"]},{"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/1810/366969"]},{"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":["immunoediting"]}]},{"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/37ce1be9-9382-4436-9c16-958d9ad4dcdd/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.17863/CAM.107681"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/02ea7ce4-80e5-4719-bd33-385302575343/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Immunoediting describes the process in tumour development whereby tumours evolve to avoid the immune system. 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An over-expression screen was performed to attempt to identify key genes involved in immunoedited tumour escape *in vivo*. Finally, a collection of bioinformatic tools were developed to perform process-based analysis of The Cancer Genome Atlas. These tools can suggest hypotheses of gene function and regulatory mechanisms and explore the pathological significance of gene expression signatures in human cancers. These tools are publicly available as an online web-tool. 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