{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10719"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10719","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Targeting and Modeling Immune Resistance in Lung Cancer","abstract":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_html":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_has_math":false,"creators":["Zhu, Mingrui"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Kittler, Ralf","Chen, Zhijian J.","Johnson, Jane E.","Minna, John D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-09-08T21:53:38Z","date_published":"2025-09-08T21:53:38Z","updated_at":"2026-07-24T05:52:13Z","subjects":["Immunotherapy","Lung Neoplasms","Small Cell Lung Carcinoma","Tumor Escape","Immunity, Innate"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1535537233"],"render_values":[{"text":"1535537233","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10719","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kittler, Ralf","Chen, Zhijian J.","Johnson, Jane E.","Minna, John D."]},{"key":"dc:creator","label":"Author","values":["Zhu, Mingrui"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-09-08T21:53:38Z","2023-08","August 2023"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunotherapy","Lung Neoplasms","Small Cell Lung Carcinoma","Tumor Escape","Immunity, Innate"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10719","1535537233"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Lung cancer causes most cancer-associated death both in U.S. and worldwide. Immune checkpoint blockade has achieved durable therapeutic effects in some lung cancer patients. The mechanism of immune escape in lung cancer merits further investigation to improve the efficacy of immune checkpoint blockade and other treatments. This thesis is focused on targeting innate immune resistance in small cell lung cancer (SCLC) and modeling human non-small cell lung cancer (NSCLC) in genetically engineered mouse models (GEMMs). I observed that SCLC escapes from innate immune surveillance by down-regulating NK cell-activating ligands. Histone deacetylase (HDAC) inhibitor could restore expression of NK cell-activating ligands and trigger anti-tumor immunity in vivo. HDAC inhibitors can be potential therapeutics for SCLC. Besides, I generated a NSCLC GEMM with high tumor mutational burden (TMB) by incorporating PoleP286R. PoleP286R GEMM with wildtype p53 is sensitive to immune checkpoint blockade (ICB). Loss of p53 and tumor heterogeneity contributed to immune escape in this high TMB mouse model. This ICB-sensitive, high TMB model can be utilized to explore novel immunotherapy and study novel mechanism of immune resistance of NSCLC."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Targeting and Modeling Immune Resistance in Lung Cancer"]}]}],"canonical_facts":{"dc:contributor":["Kittler, Ralf","Chen, Zhijian J.","Johnson, Jane E.","Minna, John D."],"dc:creator":["Zhu, Mingrui"],"dc:date":["2025-09-08T21:53:38Z","2023-08","August 2023"],"dc:description":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Lung cancer causes most cancer-associated death both in U.S. and worldwide. Immune checkpoint blockade has achieved durable therapeutic effects in some lung cancer patients. The mechanism of immune escape in lung cancer merits further investigation to improve the efficacy of immune checkpoint blockade and other treatments. This thesis is focused on targeting innate immune resistance in small cell lung cancer (SCLC) and modeling human non-small cell lung cancer (NSCLC) in genetically engineered mouse models (GEMMs). I observed that SCLC escapes from innate immune surveillance by down-regulating NK cell-activating ligands. Histone deacetylase (HDAC) inhibitor could restore expression of NK cell-activating ligands and trigger anti-tumor immunity in vivo. HDAC inhibitors can be potential therapeutics for SCLC. Besides, I generated a NSCLC GEMM with high tumor mutational burden (TMB) by incorporating PoleP286R. PoleP286R GEMM with wildtype p53 is sensitive to immune checkpoint blockade (ICB). Loss of p53 and tumor heterogeneity contributed to immune escape in this high TMB mouse model. This ICB-sensitive, high TMB model can be utilized to explore novel immunotherapy and study novel mechanism of immune resistance of NSCLC."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10719","1535537233"],"dc:language":["en"],"dc:subject":["Immunotherapy","Lung Neoplasms","Small Cell Lung Carcinoma","Tumor Escape","Immunity, Innate"],"dc:title":["Targeting and Modeling Immune Resistance in Lung Cancer"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:13Z"}