{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79852"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79852","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Understanding How Adrenergic Stess Signaling Impacts the Anti-Tumor Immune Response and the Efficacy of Checkpoint Inhibitors in Murine Tumor Models","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Bucsek, Mark; 0000-0002-8452-2898"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Repasky, Elizabeth","Microbiology and Immunology"],"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","medicine"],"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/10477/79852","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Repasky, Elizabeth","Microbiology and Immunology"]},{"key":"dc:creator","label":"Author","values":["Bucsek, Mark; 0000-0002-8452-2898"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-30T15:10:29Z","2019","2018-12-04 13:03:41"]},{"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","medicine"]}]},{"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/10477/79852"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Recent work from our laboratory has shown that anti-tumor immunity is suppressed, while tumor growth is accelerated, in mice housed at standard temperatures (ST; 22°C) which could be reversed by housing mice at warmer, thermoneutral temperatures (TT; 30°C). However, the mechanisms causing this immune impairment and enhancement of tumor growth at ST were not identified. Cold stress is mediated specifically by activation of the sympathetic nervous system and the release of norepinephrine (NE), which is highly suppressive when signaling through β-adrenergic receptors (β-ARs) on immune cells. However, there is little information on how the anti-tumor immune response is influenced by NE. We found that NE levels are significantly elevated in tumor-bearing mice housed at ST compared to TT, which led us to hypothesize that chronic stress induced by cool housing temperatures increases β-AR signaling that dampens the anti-tumor immune response and the efficacy of anti-cancer therapies such as immune checkpoint blockade and radiation. We used physiologic (housing temperature; ST and TT), pharmacologic blockade (β-blockers), and genetic strategies (β2-AR knockout mice; Adrb2-/-) to modulate β-AR signaling levels in immune-competent and SCID mice in addition to mice depleted of CD8+ and CD4+ T cells bearing 4T1 or B16-OVA tumors. At the experimental endpoint, we used flow cytometry to analyze tumor infiltrating immune cells. In our studies using anti-PD-1 checkpoint blockade, we gave mice 6 doses of anti-PD-1 with or without propranolol beginning the day after tumors became detectable... Taken together, these data indicate that elevated β-AR stress signaling caused by cool housing temperatures impairs the endogenous anti-tumor immune response in a CD8+ T cell dependent manner. Furthermore, we determined that β-AR signaling suppresses the response of multiple tumor models to anti-PD-1 checkpoint blockade. In addition, our radiation work revealed that β-blockade was also able to improve responses to radiation therapy by both sensitizing tumor cells to radiation induced death and improving the subsequent anti-tumor immune response. Taken together, this work supports the clinical assessment of using FDA approved β-blockers to improve patient responses to both immunotherapies and radiation therapy."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Understanding How Adrenergic Stess Signaling Impacts the Anti-Tumor Immune Response and the Efficacy of Checkpoint Inhibitors in Murine Tumor Models"]}]}],"canonical_facts":{"dc:contributor":["Repasky, Elizabeth","Microbiology and Immunology"],"dc:creator":["Bucsek, Mark; 0000-0002-8452-2898"],"dc:date":["2019-07-30T15:10:29Z","2019","2018-12-04 13:03:41"],"dc:description":["Ph.D.","Recent work from our laboratory has shown that anti-tumor immunity is suppressed, while tumor growth is accelerated, in mice housed at standard temperatures (ST; 22°C) which could be reversed by housing mice at warmer, thermoneutral temperatures (TT; 30°C). However, the mechanisms causing this immune impairment and enhancement of tumor growth at ST were not identified. Cold stress is mediated specifically by activation of the sympathetic nervous system and the release of norepinephrine (NE), which is highly suppressive when signaling through β-adrenergic receptors (β-ARs) on immune cells. However, there is little information on how the anti-tumor immune response is influenced by NE. We found that NE levels are significantly elevated in tumor-bearing mice housed at ST compared to TT, which led us to hypothesize that chronic stress induced by cool housing temperatures increases β-AR signaling that dampens the anti-tumor immune response and the efficacy of anti-cancer therapies such as immune checkpoint blockade and radiation. We used physiologic (housing temperature; ST and TT), pharmacologic blockade (β-blockers), and genetic strategies (β2-AR knockout mice; Adrb2-/-) to modulate β-AR signaling levels in immune-competent and SCID mice in addition to mice depleted of CD8+ and CD4+ T cells bearing 4T1 or B16-OVA tumors. At the experimental endpoint, we used flow cytometry to analyze tumor infiltrating immune cells. In our studies using anti-PD-1 checkpoint blockade, we gave mice 6 doses of anti-PD-1 with or without propranolol beginning the day after tumors became detectable... Taken together, these data indicate that elevated β-AR stress signaling caused by cool housing temperatures impairs the endogenous anti-tumor immune response in a CD8+ T cell dependent manner. Furthermore, we determined that β-AR signaling suppresses the response of multiple tumor models to anti-PD-1 checkpoint blockade. In addition, our radiation work revealed that β-blockade was also able to improve responses to radiation therapy by both sensitizing tumor cells to radiation induced death and improving the subsequent anti-tumor immune response. Taken together, this work supports the clinical assessment of using FDA approved β-blockers to improve patient responses to both immunotherapies and radiation therapy."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79852"],"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","medicine"],"dc:title":["Understanding How Adrenergic Stess Signaling Impacts the Anti-Tumor Immune Response and the Efficacy of Checkpoint Inhibitors in Murine Tumor Models"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:19Z"}