{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79332"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79332","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Mature Neutrophils Suppress T Cell Immunity in the Tumor Microenvironment of Advanced Epithelial Ovarian Cancer","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Singel, Kelly; 0000-0002-8053-4736"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Segal, Brahm","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-04-04T20:30:24Z","date_published":"2019-04-04T20:30:24Z","updated_at":"2026-07-27T19:05:14Z","subjects":["immunology","oncology","micro"],"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/10477/79332","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Segal, Brahm","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Singel, Kelly; 0000-0002-8053-4736"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-04-04T20:30:24Z","2019","2018-09-07 15:34:47"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["immunology","oncology","micro"]}]},{"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/10477/79332"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","The presence of white cells within tumors was observed in the 19th century by Rudolf Virchow and raised the notion that inflammation may play a role in cancer. It is now recognized that inflammation plays critical roles at multiple stages of cancer: initiation, growth, metastasis, and response to therapy. Neutrophils and platelets are first responders to traumatic injury, and are critical to control bleeding, prevent infection, and promote repair of damaged tissue. However, conditions within the tumor microenvironment—hypoxia, nutrient starvation, cellular proliferation and necrosis—can also lead to the recruitment and activation of neutrophils and platelets, which can accelerate tumor progression. Neutrophil recruitment and activation can have broad effects on tumor cells and the microenvironment that can either promote control or progression of tumor. While neutrophils can have direct tumoricidal activity, they can promote metastasis by cross signaling with platelets resulting in thrombosis and creating a niche that facilitates tumor cell seeding at distant sites. Although critical for host defense, neutrophils can suppress T cell responses. While this suppressive function may be beneficial in certain contexts (e.g., protection from autoimmunity), in the context of cancer, these suppressive responses can be barriers to anti-tumor immunity. Granulocytic myeloid-derived suppressor cells are an immature heterogeneous myeloid population expanded in the marrow by tumor-derived factors that accelerate tumor progression by suppressing T cell immunity and promoting angiogenesis. In addition, tumor-associated neutrophils induced by transforming growth factor-beta suppress anti-tumor immunity in murine models. Gaps in the field exist in our understanding of the role of mature neutrophils as suppressor cells in the tumor microenvironment, and the major neutrophil effector functions that drive this suppressor phenotype. By elucidating the biology of neutrophils as suppressor cells in the tumor microenvironment, we may develop therapeutic approaches to abrogate this suppressor phenotype and promote durable anti-tumor immunity.Despite advances in surgery and chemotherapy over the past two decades, epithelial ovarian cancer is still the leading cause of death from gynecological malignancies and the second most common gynecological cancer in the United States. It is typically diagnosed at advanced stages, presenting with peritoneal metastases and ascites. Although epithelial ovarian cancer is an immunogenic tumor, checkpoint inhibitor therapy has been largely ineffective, raising the possibility of suppressor pathways as barriers to immunotherapy. Our overall hypothesis is that in advanced epithelial ovarian cancer, mature neutrophils are recruited to the tumor microenvironment by products of cellular injury and cytokine responses, where they promote tumor progression by activation of pro-thrombogenic pathways and suppression of T cell responses required for anti-tumor immunity. Further, we hypothesize that the neutrophil suppressor phenotype will be reversible and present opportunities for therapeutic intervention for patients with advanced epithelial ovarian cancer.The body of work presented here point to neutrophils, which have evolved to defend against infection, eliciting off-target effects in the tumor microenvironment that can obstruct durable anti-tumor immunity and accelerate tumor progression. As a result of this dissertation work, we gained mechanistic insight into neutrophils recruited to the epithelial ovarian cancer microenvironment driving tumor progression and identified new therapeutic targets."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Mature Neutrophils Suppress T Cell Immunity in the Tumor Microenvironment of Advanced Epithelial Ovarian Cancer"]}]}],"canonical_facts":{"dc:contributor":["Segal, Brahm","Roswell Park"],"dc:creator":["Singel, Kelly; 0000-0002-8053-4736"],"dc:date":["2019-04-04T20:30:24Z","2019","2018-09-07 15:34:47"],"dc:description":["Ph.D.","The presence of white cells within tumors was observed in the 19th century by Rudolf Virchow and raised the notion that inflammation may play a role in cancer. It is now recognized that inflammation plays critical roles at multiple stages of cancer: initiation, growth, metastasis, and response to therapy. Neutrophils and platelets are first responders to traumatic injury, and are critical to control bleeding, prevent infection, and promote repair of damaged tissue. However, conditions within the tumor microenvironment—hypoxia, nutrient starvation, cellular proliferation and necrosis—can also lead to the recruitment and activation of neutrophils and platelets, which can accelerate tumor progression. Neutrophil recruitment and activation can have broad effects on tumor cells and the microenvironment that can either promote control or progression of tumor. While neutrophils can have direct tumoricidal activity, they can promote metastasis by cross signaling with platelets resulting in thrombosis and creating a niche that facilitates tumor cell seeding at distant sites. Although critical for host defense, neutrophils can suppress T cell responses. While this suppressive function may be beneficial in certain contexts (e.g., protection from autoimmunity), in the context of cancer, these suppressive responses can be barriers to anti-tumor immunity. Granulocytic myeloid-derived suppressor cells are an immature heterogeneous myeloid population expanded in the marrow by tumor-derived factors that accelerate tumor progression by suppressing T cell immunity and promoting angiogenesis. In addition, tumor-associated neutrophils induced by transforming growth factor-beta suppress anti-tumor immunity in murine models. Gaps in the field exist in our understanding of the role of mature neutrophils as suppressor cells in the tumor microenvironment, and the major neutrophil effector functions that drive this suppressor phenotype. By elucidating the biology of neutrophils as suppressor cells in the tumor microenvironment, we may develop therapeutic approaches to abrogate this suppressor phenotype and promote durable anti-tumor immunity.Despite advances in surgery and chemotherapy over the past two decades, epithelial ovarian cancer is still the leading cause of death from gynecological malignancies and the second most common gynecological cancer in the United States. It is typically diagnosed at advanced stages, presenting with peritoneal metastases and ascites. Although epithelial ovarian cancer is an immunogenic tumor, checkpoint inhibitor therapy has been largely ineffective, raising the possibility of suppressor pathways as barriers to immunotherapy. Our overall hypothesis is that in advanced epithelial ovarian cancer, mature neutrophils are recruited to the tumor microenvironment by products of cellular injury and cytokine responses, where they promote tumor progression by activation of pro-thrombogenic pathways and suppression of T cell responses required for anti-tumor immunity. Further, we hypothesize that the neutrophil suppressor phenotype will be reversible and present opportunities for therapeutic intervention for patients with advanced epithelial ovarian cancer.The body of work presented here point to neutrophils, which have evolved to defend against infection, eliciting off-target effects in the tumor microenvironment that can obstruct durable anti-tumor immunity and accelerate tumor progression. As a result of this dissertation work, we gained mechanistic insight into neutrophils recruited to the epithelial ovarian cancer microenvironment driving tumor progression and identified new therapeutic targets."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79332"],"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","oncology","micro"],"dc:title":["Mature Neutrophils Suppress T Cell Immunity in the Tumor Microenvironment of Advanced Epithelial Ovarian Cancer"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:14Z"}