{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/127425"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/127425","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Re-education of myeloid immune cells to reduce regulatory T cell expansion and impede breast cancer progression","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","abstract_has_math":false,"creators":["Vidana Gamage, Hashni Epa"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular & Integrative Physi","degree_department":null,"school":null,"contributors":["Nelson, Erik R","Ridlon, Jason M","Hergenrother, Paul J","Raetzman, Lori T"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-08-02","date_published":"2024-08-02","updated_at":"2026-07-22T22:25:04Z","subjects":["Cholesterol","Dshn-ome","Nuclear Receptor","Small Heterodimer Partner","Treg."],"languages":["en","eng"],"rights":["©2024 Hashni Epa Vidana Gamage"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/127425","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nelson, Erik R","Ridlon, Jason M","Hergenrother, Paul J","Raetzman, Lori T"]},{"key":"dc:creator","label":"Author","values":["Vidana Gamage, Hashni Epa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-08-02","2024-12"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular & Integrative Physi"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cholesterol","Dshn-ome","Nuclear Receptor","Small Heterodimer Partner","Treg."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["©2024 Hashni Epa Vidana Gamage"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/127425"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","The student, Hashni Epa Vidana Gamage, accepted the attached license on 2024-07-30 at 11:01.","The student, Hashni Epa Vidana Gamage, submitted this Dissertation for approval on 2024-07-30 at 11:10.","This Dissertation was approved for publication on 2024-08-02 at 11:17.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21175 on 2025-03-28 at 14:52:59","Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, the survival for this stage of the disease remains very low. Stimulating patients own immune systems against cancer cells has shown incredible curative potential in certain types of cancers and patients such as melanoma. However, immune checkpoint blockade (ICB) which works through T cells has had limited efficacy in breast cancer. Therefore, there is considerable interest in alternate strategies to promote an anti-cancer immune response. Infiltration of immune-suppressive regulatory T cells (Treg) to the tumor microenvironment (TME) is associated with resistance to ICB. Tregs are a subset of CD4+ T cells known to be highly immune suppressive and associated with poor therapeutic response. Interestingly, within human breast tumors, NR0B2, a protein involved in cholesterol homeostasis, is inversely associated with FOXP3, a marker of Tregs. Myeloid intrinsic NR0B2 serves to decrease many aspects of the NLRP3 inflammasome, ultimately resulting in decreased IL1β; IL1β driving Treg expansion. Importantly, mice lacking NR0B2 exhibit accelerated tumor growth. Furthermore, we have developed NR0B2 as a potential therapeutic target. Small molecule agonists, including one developed here, reduced Treg expansion, reduced metastatic growth, and improved the efficacy of ICB. Together these findings demonstrate NR0B2 as a target to ‘re-educate’ myeloid immune cells and its potential utility in enhancing ICB. This work identifies NR0B2 as a target to re-educate myeloid immune cells and a novel ligand with significant anti-tumor efficacy in preclinical models."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Re-education of myeloid immune cells to reduce regulatory T cell expansion and impede breast cancer progression"]}]}],"canonical_facts":{"dc:contributor":["Nelson, Erik R","Ridlon, Jason M","Hergenrother, Paul J","Raetzman, Lori T"],"dc:creator":["Vidana Gamage, Hashni Epa"],"dc:date":["2024-08-02","2024-12"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","The student, Hashni Epa Vidana Gamage, accepted the attached license on 2024-07-30 at 11:01.","The student, Hashni Epa Vidana Gamage, submitted this Dissertation for approval on 2024-07-30 at 11:10.","This Dissertation was approved for publication on 2024-08-02 at 11:17.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21175 on 2025-03-28 at 14:52:59","Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, the survival for this stage of the disease remains very low. Stimulating patients own immune systems against cancer cells has shown incredible curative potential in certain types of cancers and patients such as melanoma. However, immune checkpoint blockade (ICB) which works through T cells has had limited efficacy in breast cancer. Therefore, there is considerable interest in alternate strategies to promote an anti-cancer immune response. Infiltration of immune-suppressive regulatory T cells (Treg) to the tumor microenvironment (TME) is associated with resistance to ICB. Tregs are a subset of CD4+ T cells known to be highly immune suppressive and associated with poor therapeutic response. Interestingly, within human breast tumors, NR0B2, a protein involved in cholesterol homeostasis, is inversely associated with FOXP3, a marker of Tregs. Myeloid intrinsic NR0B2 serves to decrease many aspects of the NLRP3 inflammasome, ultimately resulting in decreased IL1β; IL1β driving Treg expansion. Importantly, mice lacking NR0B2 exhibit accelerated tumor growth. Furthermore, we have developed NR0B2 as a potential therapeutic target. Small molecule agonists, including one developed here, reduced Treg expansion, reduced metastatic growth, and improved the efficacy of ICB. Together these findings demonstrate NR0B2 as a target to ‘re-educate’ myeloid immune cells and its potential utility in enhancing ICB. This work identifies NR0B2 as a target to re-educate myeloid immune cells and a novel ligand with significant anti-tumor efficacy in preclinical models."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/127425"],"dc:language":["en","eng"],"dc:rights":["©2024 Hashni Epa Vidana Gamage"],"dc:subject":["Cholesterol","Dshn-ome","Nuclear Receptor","Small Heterodimer Partner","Treg."],"dc:title":["Re-education of myeloid immune cells to reduce regulatory T cell expansion and impede breast cancer progression"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Molecular & Integrative Physi"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:04Z"}