{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79851"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79851","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Tumor-Derived Thymic Stromal Lymphopoietin Modulates Alveolar Macrophage Function in Neoplastic Disease","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Burkard-Mandel, Lauren"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Abrams, Scott","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-30T15:10:29Z","date_published":"2019-07-30T15:10:29Z","updated_at":"2026-07-27T19:05:19Z","subjects":["immunology","microbiology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79851","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Abrams, Scott","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Burkard-Mandel, Lauren"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-30T15:10:29Z","2019","2018-03-12 10:52:41"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["immunology","microbiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79851"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Ordinarily, macrophages play critical roles in host defense, including neoplasia. Within a tumor, though, macrophages are potentially ‘plastic’ and can transition between distinct functional states largely influenced by the inflammatory microenvironment. Macrophages can adopt an ‘M1’ phenotype, which is thought to be effective in antitumor immunity, or an ‘M2’ phenotype which can support metastatic progression. Moreover, tissue-resident macrophages have been shown to play significant roles in metastatic environments but this cell population remains largely understudied. The role of macrophages in metastasis is especially important in solid tumor biology, as patients are unlikely to succumb to primary disease, but rather to metastasis. Despite the fact that macrophages can assume multiple functional states, the mechanisms that oversee such behavioral characteristics remain incompletely understood. It is well-recognized, however, that cytokines such as IL-4, IL-13 and IL-10, are classic drivers of M2 macrophages, but beyond that much less is known. Here, we hypothesize a novel role for thymic stromal lymphopoietin (TSLP) in metastasis by exacerbating M2-like responses. This reflects the rationale that TSLP can intensify M2-macrophage activities in allergy models and the more recent findings that TSLP is found in mouse and human cancer settings although its precise role remains unsettled. Based on this rationale, we hypothesize that TSLP plays an unrecognized role in metastasis by influencing the macrophage-tumor interaction. To test this hypothesis, we made use of a well-characterized mouse mammary tumor model of spontaneous lung metastasis, termed 4T1. Our data demonstrate that tumors represent a significant source of TSLP, which enhances the propensity to lung metastasis. We have shown that the adaptive immune response is not responsible for this metastatic outcome as similar findings are observed in SCID or athymic hosts. Importantly, depletion of alveolar macrophages diminishes the pro-metastatic effects of TSLP, indicating that this is a key cell type by which TSLP exerts its metastatic effects. In support of this finding, TSLP increases the pro-tumorigenic phenotype of alveolar macrophages, as shown by an increase in an angiogenic and invasive gene signature. TSLP does not alter MDSC accumulation in tumor-bearing mice, supporting our data that macrophages are likely major mediators of metastasis in these models. This is enforced by data demonstrating that TSLP treated alveolar macrophages do not suppress T cell proliferation. Altogether, these data suggest that TSLP plays previously undescribed roles in metastasis by altering the behavior of alveolar macrophage-dependent mechanisms and these novel findings have important implications for patient prognosis or treatment."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Tumor-Derived Thymic Stromal Lymphopoietin Modulates Alveolar Macrophage Function in Neoplastic Disease"]}]}],"canonical_facts":{"dc:contributor":["Abrams, Scott","Roswell Park"],"dc:creator":["Burkard-Mandel, Lauren"],"dc:date":["2019-07-30T15:10:29Z","2019","2018-03-12 10:52:41"],"dc:description":["Ph.D.","Ordinarily, macrophages play critical roles in host defense, including neoplasia. Within a tumor, though, macrophages are potentially ‘plastic’ and can transition between distinct functional states largely influenced by the inflammatory microenvironment. Macrophages can adopt an ‘M1’ phenotype, which is thought to be effective in antitumor immunity, or an ‘M2’ phenotype which can support metastatic progression. Moreover, tissue-resident macrophages have been shown to play significant roles in metastatic environments but this cell population remains largely understudied. The role of macrophages in metastasis is especially important in solid tumor biology, as patients are unlikely to succumb to primary disease, but rather to metastasis. Despite the fact that macrophages can assume multiple functional states, the mechanisms that oversee such behavioral characteristics remain incompletely understood. It is well-recognized, however, that cytokines such as IL-4, IL-13 and IL-10, are classic drivers of M2 macrophages, but beyond that much less is known. Here, we hypothesize a novel role for thymic stromal lymphopoietin (TSLP) in metastasis by exacerbating M2-like responses. This reflects the rationale that TSLP can intensify M2-macrophage activities in allergy models and the more recent findings that TSLP is found in mouse and human cancer settings although its precise role remains unsettled. Based on this rationale, we hypothesize that TSLP plays an unrecognized role in metastasis by influencing the macrophage-tumor interaction. To test this hypothesis, we made use of a well-characterized mouse mammary tumor model of spontaneous lung metastasis, termed 4T1. Our data demonstrate that tumors represent a significant source of TSLP, which enhances the propensity to lung metastasis. We have shown that the adaptive immune response is not responsible for this metastatic outcome as similar findings are observed in SCID or athymic hosts. Importantly, depletion of alveolar macrophages diminishes the pro-metastatic effects of TSLP, indicating that this is a key cell type by which TSLP exerts its metastatic effects. In support of this finding, TSLP increases the pro-tumorigenic phenotype of alveolar macrophages, as shown by an increase in an angiogenic and invasive gene signature. TSLP does not alter MDSC accumulation in tumor-bearing mice, supporting our data that macrophages are likely major mediators of metastasis in these models. This is enforced by data demonstrating that TSLP treated alveolar macrophages do not suppress T cell proliferation. Altogether, these data suggest that TSLP plays previously undescribed roles in metastasis by altering the behavior of alveolar macrophage-dependent mechanisms and these novel findings have important implications for patient prognosis or treatment."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79851"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["immunology","microbiology"],"dc:title":["Tumor-Derived Thymic Stromal Lymphopoietin Modulates Alveolar Macrophage Function in Neoplastic Disease"],"dc:type":["Dissertation","Text"]},"updated_at":"2026-07-27T19:05:19Z"}