{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/64191"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/64191","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"Regulation of Protective B cell Anti-Tumor Responses","abstract":"The role of B cells in tumor progression is complex and often overlooked. Specifically, little is known about the extent to which the specialized populations of innate-like B-1a and B-1b cells participate in and contribute to the anti-tumor immune response. The totality of work presented in this document demonstrates novel roles for B-1 cells in the anti-tumor response. B-1a cells are important for the innate response against peritoneal carcinomatosis through the production of natural antibody (nAb) that recognizes tumor cells. The protective B-1a cell anti-tumor response is stimulated by pathogen-associated molecular patterns derived from bacteria. The B-1b cell subpopulation plays an important role in the adaptive humoral response against tumors expressing tumor associated carbohydrate antigens (TACAs). B-1b cells specifically contribute to the antibody response to the TACA, Tn. TACAs are normally masked on healthy cells, which make these carbohydrate antigens ideal targets for the anti-tumor immune response. Thus, there is great interest in developing TACA-based vaccines. Unfortunately, this effort has been hindered by a lack of success in clinical trials. This is potentially due to complex immuno-regulatory mechanisms which ultimately serve to inhibit the protective humoral response against TACA-expressing tumors. The immuno-inhibitory molecule PD-1 is expressed by antigen-activated B cells and suppresses B cell expansion and mucin- and Tn-specific antibody production. These antibodies contribute to the anti-tumor response via a complement-dependent mechanism. Immune-regulation of humoral responses to sialylated TACAs is governed by the inhibitory molecule CD22, which is constitutively expressed by B cells. CD22, is a sialic acid-binding, Ig-like, lectin receptor (Siglec), and was found to significantly suppress antigen-specific antibody responses to mucins bearing sialylated TACAs. Inhibition of CD22 binding of sialic acids using monoclonal antibody blockade during immunization significantly increased anti-mucin antibody production and subsequent protection in mouse models of peritoneal carcinomatosis and prostate cancer. Collectively, the work presented here provides a greater understanding of the intricate mechanisms regulating the humoral response to TACAs and the unique role of different B cell subsets in the anti-tumor response. Finally, it highlights potential novel therapeutic strategies to promote B cell anti-tumor immune responses in the treatment of cancer.","abstract_html":"The role of B cells in tumor progression is complex and often overlooked. Specifically, little is known about the extent to which the specialized populations of innate-like B-1a and B-1b cells participate in and contribute to the anti-tumor immune response. The totality of work presented in this document demonstrates novel roles for B-1 cells in the anti-tumor response. B-1a cells are important for the innate response against peritoneal carcinomatosis through the production of natural antibody (nAb) that recognizes tumor cells. The protective B-1a cell anti-tumor response is stimulated by pathogen-associated molecular patterns derived from bacteria. The B-1b cell subpopulation plays an important role in the adaptive humoral response against tumors expressing tumor associated carbohydrate antigens (TACAs). B-1b cells specifically contribute to the antibody response to the TACA, Tn. TACAs are normally masked on healthy cells, which make these carbohydrate antigens ideal targets for the anti-tumor immune response. Thus, there is great interest in developing TACA-based vaccines. Unfortunately, this effort has been hindered by a lack of success in clinical trials. This is potentially due to complex immuno-regulatory mechanisms which ultimately serve to inhibit the protective humoral response against TACA-expressing tumors. The immuno-inhibitory molecule PD-1 is expressed by antigen-activated B cells and suppresses B cell expansion and mucin- and Tn-specific antibody production. These antibodies contribute to the anti-tumor response via a complement-dependent mechanism. Immune-regulation of humoral responses to sialylated TACAs is governed by the inhibitory molecule CD22, which is constitutively expressed by B cells. CD22, is a sialic acid-binding, Ig-like, lectin receptor (Siglec), and was found to significantly suppress antigen-specific antibody responses to mucins bearing sialylated TACAs. Inhibition of CD22 binding of sialic acids using monoclonal antibody blockade during immunization significantly increased anti-mucin antibody production and subsequent protection in mouse models of peritoneal carcinomatosis and prostate cancer. Collectively, the work presented here provides a greater understanding of the intricate mechanisms regulating the humoral response to TACAs and the unique role of different B cell subsets in the anti-tumor response. Finally, it highlights potential novel therapeutic strategies to promote B cell anti-tumor immune responses in the treatment of cancer.","abstract_has_math":false,"creators":["Haro, Marcela"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-27T22:02:05Z","subjects":["B-1 cells"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/64191","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Haro, Marcela"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-01-14T09:35:28Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-12-15T09:30:12Z"]},{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["B-1 cells"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10339/64191"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The role of B cells in tumor progression is complex and often overlooked. Specifically, little is known about the extent to which the specialized populations of innate-like B-1a and B-1b cells participate in and contribute to the anti-tumor immune response. The totality of work presented in this document demonstrates novel roles for B-1 cells in the anti-tumor response. B-1a cells are important for the innate response against peritoneal carcinomatosis through the production of natural antibody (nAb) that recognizes tumor cells. The protective B-1a cell anti-tumor response is stimulated by pathogen-associated molecular patterns derived from bacteria. The B-1b cell subpopulation plays an important role in the adaptive humoral response against tumors expressing tumor associated carbohydrate antigens (TACAs). B-1b cells specifically contribute to the antibody response to the TACA, Tn. TACAs are normally masked on healthy cells, which make these carbohydrate antigens ideal targets for the anti-tumor immune response. Thus, there is great interest in developing TACA-based vaccines. Unfortunately, this effort has been hindered by a lack of success in clinical trials. This is potentially due to complex immuno-regulatory mechanisms which ultimately serve to inhibit the protective humoral response against TACA-expressing tumors. The immuno-inhibitory molecule PD-1 is expressed by antigen-activated B cells and suppresses B cell expansion and mucin- and Tn-specific antibody production. These antibodies contribute to the anti-tumor response via a complement-dependent mechanism. Immune-regulation of humoral responses to sialylated TACAs is governed by the inhibitory molecule CD22, which is constitutively expressed by B cells. CD22, is a sialic acid-binding, Ig-like, lectin receptor (Siglec), and was found to significantly suppress antigen-specific antibody responses to mucins bearing sialylated TACAs. Inhibition of CD22 binding of sialic acids using monoclonal antibody blockade during immunization significantly increased anti-mucin antibody production and subsequent protection in mouse models of peritoneal carcinomatosis and prostate cancer. Collectively, the work presented here provides a greater understanding of the intricate mechanisms regulating the humoral response to TACAs and the unique role of different B cell subsets in the anti-tumor response. Finally, it highlights potential novel therapeutic strategies to promote B cell anti-tumor immune responses in the treatment of cancer."]},{"key":"dc:title","label":"Title","values":["Regulation of Protective B cell Anti-Tumor Responses"]}]}],"canonical_facts":{"dc:creator":["Haro, Marcela"],"dc:date.accessioned":["2017-01-14T09:35:28Z"],"dc:date.available":["2021-12-15T09:30:12Z"],"dc:date.issued":["2016"],"dc:description.abstract":["The role of B cells in tumor progression is complex and often overlooked. Specifically, little is known about the extent to which the specialized populations of innate-like B-1a and B-1b cells participate in and contribute to the anti-tumor immune response. The totality of work presented in this document demonstrates novel roles for B-1 cells in the anti-tumor response. B-1a cells are important for the innate response against peritoneal carcinomatosis through the production of natural antibody (nAb) that recognizes tumor cells. The protective B-1a cell anti-tumor response is stimulated by pathogen-associated molecular patterns derived from bacteria. The B-1b cell subpopulation plays an important role in the adaptive humoral response against tumors expressing tumor associated carbohydrate antigens (TACAs). B-1b cells specifically contribute to the antibody response to the TACA, Tn. TACAs are normally masked on healthy cells, which make these carbohydrate antigens ideal targets for the anti-tumor immune response. Thus, there is great interest in developing TACA-based vaccines. Unfortunately, this effort has been hindered by a lack of success in clinical trials. This is potentially due to complex immuno-regulatory mechanisms which ultimately serve to inhibit the protective humoral response against TACA-expressing tumors. The immuno-inhibitory molecule PD-1 is expressed by antigen-activated B cells and suppresses B cell expansion and mucin- and Tn-specific antibody production. These antibodies contribute to the anti-tumor response via a complement-dependent mechanism. Immune-regulation of humoral responses to sialylated TACAs is governed by the inhibitory molecule CD22, which is constitutively expressed by B cells. CD22, is a sialic acid-binding, Ig-like, lectin receptor (Siglec), and was found to significantly suppress antigen-specific antibody responses to mucins bearing sialylated TACAs. Inhibition of CD22 binding of sialic acids using monoclonal antibody blockade during immunization significantly increased anti-mucin antibody production and subsequent protection in mouse models of peritoneal carcinomatosis and prostate cancer. Collectively, the work presented here provides a greater understanding of the intricate mechanisms regulating the humoral response to TACAs and the unique role of different B cell subsets in the anti-tumor response. Finally, it highlights potential novel therapeutic strategies to promote B cell anti-tumor immune responses in the treatment of cancer."],"dc:identifier.uri":["http://hdl.handle.net/10339/64191"],"dc:language.iso":["en"],"dc:publisher":["Wake Forest University"],"dc:subject":["B-1 cells"],"dc:title":["Regulation of Protective B cell Anti-Tumor Responses"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T22:02:05Z"}