{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/38779"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/38779","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"The association of tumor-induced changes in macrophage phenotype with immunosuppressive functions","abstract":"During tumor growth there are a series of phenotypic and functional changes that occur in macrophages (MΦ) that ultimately lead to the immunosuppression of the tumor-bearing host (TBH). To investigate the phenotypic changes of MΦ during tumor growth, we examined the expression of the MΦ surface antigens, Mac-1, Mac-2, Mac-3, and Ia on peritoneal and splenic MΦ. In the peritoneal cavity there was no change in the percentage of Mac-1⁺ MΦ but a decrease in the percentage of Mac-2⁺, -3⁺, and Ia⁺ MΦ during tumor growth. In addition, three distinctly sized populations of peritoneal MΦ, showing differential antigen expression, also shifted during tumor growth. In the peritoneal cavity there was a decrease in the percentage of MΦ co-expressing the Mac-2, -3, and Ia antigens, leading to a shift towards Mac-1⁺ 2⁻ 3⁻ Ia⁻ TBH MΦ. In splenic MΦ, the percentage of Mac-1⁺, -2⁺, and -3⁺ MΦ increased, while the percentage of Ia⁺ MΦ decreased. Splenic MΦ showed an increase in the percentage of MΦ co-expressing Mac-1, -2, and -3 antigens and a decrease in the percentage of MΦ co-expressing Ia, leading to a shift towards a Mac-1⁺ 2⁺ 3⁺ Ia⁻ TBH MΦ. Taken together, these data suggest that tumor growth alters the phenotype of MΦ and causes a shift in MΦ subpopulations. After measuring the phenotypic changes in MΦ during tumor growth, changes in MΦ accessory function to T cells were assessed. TBH MΦ have significantly reduced accessory activity for autoreactive T cells. This reduction is caused by decreased Ia antigen expression and increased production of the suppressor molecule, prostaglandin (PG). TBH MΦ down-regulated autoreactive T cell responsiveness to interleukin (IL)-1, IL-2, and IL-4. In addition to TBH MΦ reducing T cell responsiveness to cytokines, TBH CD4⁺ T cells alone were less responsive to the cytokines IL-1, IL-2, and IL-4. To examine the responsiveness of MΦ to activation signals, lipopolysaccharide (LPS) was incubated with normal and TBH splenic MΦ and assessed for their phenotypic, functional, and cell-cycle changes. The data showed that TBH MΦ had a decreased responsiveness to LPS. We showed that there was a shift from an Ia⁺ MΦ in the normal host to an Ia⁻ MΦ in the TBH. Concomitant with the shift in TBH MΦ Ia⁻ phenotype was a change in TBH MΦ function. Normal and TBH Ia⁻ MΦ were suppressor MΦ. TBH Ia⁻ MΦ, however, suppressed autoreactive and alloreactive CD4⁺ T cells significantly more than could their normal counterparts. Tumor growth causes quantitative and qualitative changes in Ia⁻ suppressor MΦ. Although Ia⁻ MΦ-mediated suppression seemed to be the major source of down-regulation of CD4⁺ T cells, CD8⁺ T cells were not without fault. In the TBH, there was an increase in the percentage of CD8⁺ T cells and an increase in CD8⁺ T cell-mediated suppression. In conclusion, tumor growth leads to a change in immunoregulation that causes suppression of the immune response.","abstract_html":"During tumor growth there are a series of phenotypic and functional changes that occur in macrophages (M<sub>Φ</sub>) that ultimately lead to the immunosuppression of the tumor-bearing host (TBH). To investigate the phenotypic changes of M<sub>Φ</sub> during tumor growth, we examined the expression of the M<sub>Φ</sub> surface antigens, Mac-1, Mac-2, Mac-3, and Ia on peritoneal and splenic M<sub>Φ</sub>. In the peritoneal cavity there was no change in the percentage of Mac-1⁺ M<sub>Φ</sub> but a decrease in the percentage of Mac-2⁺, -3⁺, and Ia⁺ M<sub>Φ</sub> during tumor growth. In addition, three distinctly sized populations of peritoneal M<sub>Φ</sub>, showing differential antigen expression, also shifted during tumor growth. In the peritoneal cavity there was a decrease in the percentage of M<sub>Φ</sub> co-expressing the Mac-2, -3, and Ia antigens, leading to a shift towards Mac-1⁺ 2⁻ 3⁻ Ia⁻ TBH M<sub>Φ</sub>. In splenic M<sub>Φ</sub>, the percentage of Mac-1⁺, -2⁺, and -3⁺ M<sub>Φ</sub> increased, while the percentage of Ia⁺ M<sub>Φ</sub> decreased. Splenic M<sub>Φ</sub> showed an increase in the percentage of M<sub>Φ</sub> co-expressing Mac-1, -2, and -3 antigens and a decrease in the percentage of M<sub>Φ</sub> co-expressing Ia, leading to a shift towards a Mac-1⁺ 2⁺ 3⁺ Ia⁻ TBH M<sub>Φ</sub>. Taken together, these data suggest that tumor growth alters the phenotype of M<sub>Φ</sub> and causes a shift in M<sub>Φ</sub> subpopulations. After measuring the phenotypic changes in M<sub>Φ</sub> during tumor growth, changes in M<sub>Φ</sub> accessory function to T cells were assessed. TBH M<sub>Φ</sub> have significantly reduced accessory activity for autoreactive T cells. This reduction is caused by decreased Ia antigen expression and increased production of the suppressor molecule, prostaglandin (PG). TBH M<sub>Φ</sub> down-regulated autoreactive T cell responsiveness to interleukin (IL)-1, IL-2, and IL-4. In addition to TBH M<sub>Φ</sub> reducing T cell responsiveness to cytokines, TBH CD4⁺ T cells alone were less responsive to the cytokines IL-1, IL-2, and IL-4. To examine the responsiveness of M<sub>Φ</sub> to activation signals, lipopolysaccharide (LPS) was incubated with normal and TBH splenic M<sub>Φ</sub> and assessed for their phenotypic, functional, and cell-cycle changes. The data showed that TBH M<sub>Φ</sub> had a decreased responsiveness to LPS. We showed that there was a shift from an Ia⁺ M<sub>Φ</sub> in the normal host to an Ia⁻ M<sub>Φ</sub> in the TBH. Concomitant with the shift in TBH M<sub>Φ</sub> Ia⁻ phenotype was a change in TBH M<sub>Φ</sub> function. Normal and TBH Ia⁻ M<sub>Φ</sub> were suppressor M<sub>Φ</sub>. TBH Ia⁻ M<sub>Φ</sub>, however, suppressed autoreactive and alloreactive CD4⁺ T cells significantly more than could their normal counterparts. Tumor growth causes quantitative and qualitative changes in Ia⁻ suppressor M<sub>Φ</sub>. Although Ia⁻ M<sub>Φ</sub>-mediated suppression seemed to be the major source of down-regulation of CD4⁺ T cells, CD8⁺ T cells were not without fault. In the TBH, there was an increase in the percentage of CD8⁺ T cells and an increase in CD8⁺ T cell-mediated suppression. In conclusion, tumor growth leads to a change in immunoregulation that causes suppression of the immune response.","abstract_has_math":false,"creators":["Yurochko, Andrew David"],"institution":"Virginia Tech","degree_name":"Ph. D.","degree_level":"doctoral","degree_discipline":"Microbiology and Immunology","degree_department":"Microbiology and Immunology","school":null,"contributors":[],"advisors":[],"committee_chairs":["Elgert, Klaus"],"committee_members":[],"year":1990,"date_issued":"1990","date_published":"1990","updated_at":"2026-07-22T22:20:02Z","subjects":[],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-07122007-103932"],"render_values":[{"text":"etd-07122007-103932","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/38779","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Elgert, Klaus"]},{"key":"dc:contributor.department","label":"Department","values":["Microbiology and Immunology"]},{"key":"dc:creator","label":"Author","values":["Yurochko, Andrew David"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-03-14T21:15:53Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-03-14T21:15:53Z","2007-07-12"]},{"key":"dc:date.issued","label":"Date","values":["1990"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology and Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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To investigate the phenotypic changes of MΦ during tumor growth, we examined the expression of the MΦ surface antigens, Mac-1, Mac-2, Mac-3, and Ia on peritoneal and splenic MΦ. In the peritoneal cavity there was no change in the percentage of Mac-1⁺ MΦ but a decrease in the percentage of Mac-2⁺, -3⁺, and Ia⁺ MΦ during tumor growth. In addition, three distinctly sized populations of peritoneal MΦ, showing differential antigen expression, also shifted during tumor growth. In the peritoneal cavity there was a decrease in the percentage of MΦ co-expressing the Mac-2, -3, and Ia antigens, leading to a shift towards Mac-1⁺ 2⁻ 3⁻ Ia⁻ TBH MΦ. In splenic MΦ, the percentage of Mac-1⁺, -2⁺, and -3⁺ MΦ increased, while the percentage of Ia⁺ MΦ decreased. Splenic MΦ showed an increase in the percentage of MΦ co-expressing Mac-1, -2, and -3 antigens and a decrease in the percentage of MΦ co-expressing Ia, leading to a shift towards a Mac-1⁺ 2⁺ 3⁺ Ia⁻ TBH MΦ. Taken together, these data suggest that tumor growth alters the phenotype of MΦ and causes a shift in MΦ subpopulations. After measuring the phenotypic changes in MΦ during tumor growth, changes in MΦ accessory function to T cells were assessed. TBH MΦ have significantly reduced accessory activity for autoreactive T cells. This reduction is caused by decreased Ia antigen expression and increased production of the suppressor molecule, prostaglandin (PG). TBH MΦ down-regulated autoreactive T cell responsiveness to interleukin (IL)-1, IL-2, and IL-4. In addition to TBH MΦ reducing T cell responsiveness to cytokines, TBH CD4⁺ T cells alone were less responsive to the cytokines IL-1, IL-2, and IL-4. To examine the responsiveness of MΦ to activation signals, lipopolysaccharide (LPS) was incubated with normal and TBH splenic MΦ and assessed for their phenotypic, functional, and cell-cycle changes. The data showed that TBH MΦ had a decreased responsiveness to LPS. We showed that there was a shift from an Ia⁺ MΦ in the normal host to an Ia⁻ MΦ in the TBH. Concomitant with the shift in TBH MΦ Ia⁻ phenotype was a change in TBH MΦ function. Normal and TBH Ia⁻ MΦ were suppressor MΦ. TBH Ia⁻ MΦ, however, suppressed autoreactive and alloreactive CD4⁺ T cells significantly more than could their normal counterparts. Tumor growth causes quantitative and qualitative changes in Ia⁻ suppressor MΦ. Although Ia⁻ MΦ-mediated suppression seemed to be the major source of down-regulation of CD4⁺ T cells, CD8⁺ T cells were not without fault. In the TBH, there was an increase in the percentage of CD8⁺ T cells and an increase in CD8⁺ T cell-mediated suppression. In conclusion, tumor growth leads to a change in immunoregulation that causes suppression of the immune response."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["BTD"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The association of tumor-induced changes in macrophage phenotype with immunosuppressive functions"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Elgert, Klaus"],"dc:contributor.department":["Microbiology and Immunology"],"dc:creator":["Yurochko, Andrew David"],"dc:date.accessioned":["2014-03-14T21:15:53Z"],"dc:date.available":["2014-03-14T21:15:53Z","2007-07-12"],"dc:date.issued":["1990"],"dc:description.abstract":["During tumor growth there are a series of phenotypic and functional changes that occur in macrophages (MΦ) that ultimately lead to the immunosuppression of the tumor-bearing host (TBH). To investigate the phenotypic changes of MΦ during tumor growth, we examined the expression of the MΦ surface antigens, Mac-1, Mac-2, Mac-3, and Ia on peritoneal and splenic MΦ. In the peritoneal cavity there was no change in the percentage of Mac-1⁺ MΦ but a decrease in the percentage of Mac-2⁺, -3⁺, and Ia⁺ MΦ during tumor growth. In addition, three distinctly sized populations of peritoneal MΦ, showing differential antigen expression, also shifted during tumor growth. In the peritoneal cavity there was a decrease in the percentage of MΦ co-expressing the Mac-2, -3, and Ia antigens, leading to a shift towards Mac-1⁺ 2⁻ 3⁻ Ia⁻ TBH MΦ. In splenic MΦ, the percentage of Mac-1⁺, -2⁺, and -3⁺ MΦ increased, while the percentage of Ia⁺ MΦ decreased. Splenic MΦ showed an increase in the percentage of MΦ co-expressing Mac-1, -2, and -3 antigens and a decrease in the percentage of MΦ co-expressing Ia, leading to a shift towards a Mac-1⁺ 2⁺ 3⁺ Ia⁻ TBH MΦ. Taken together, these data suggest that tumor growth alters the phenotype of MΦ and causes a shift in MΦ subpopulations. After measuring the phenotypic changes in MΦ during tumor growth, changes in MΦ accessory function to T cells were assessed. TBH MΦ have significantly reduced accessory activity for autoreactive T cells. This reduction is caused by decreased Ia antigen expression and increased production of the suppressor molecule, prostaglandin (PG). TBH MΦ down-regulated autoreactive T cell responsiveness to interleukin (IL)-1, IL-2, and IL-4. In addition to TBH MΦ reducing T cell responsiveness to cytokines, TBH CD4⁺ T cells alone were less responsive to the cytokines IL-1, IL-2, and IL-4. To examine the responsiveness of MΦ to activation signals, lipopolysaccharide (LPS) was incubated with normal and TBH splenic MΦ and assessed for their phenotypic, functional, and cell-cycle changes. The data showed that TBH MΦ had a decreased responsiveness to LPS. We showed that there was a shift from an Ia⁺ MΦ in the normal host to an Ia⁻ MΦ in the TBH. Concomitant with the shift in TBH MΦ Ia⁻ phenotype was a change in TBH MΦ function. Normal and TBH Ia⁻ MΦ were suppressor MΦ. TBH Ia⁻ MΦ, however, suppressed autoreactive and alloreactive CD4⁺ T cells significantly more than could their normal counterparts. Tumor growth causes quantitative and qualitative changes in Ia⁻ suppressor MΦ. Although Ia⁻ MΦ-mediated suppression seemed to be the major source of down-regulation of CD4⁺ T cells, CD8⁺ T cells were not without fault. In the TBH, there was an increase in the percentage of CD8⁺ T cells and an increase in CD8⁺ T cell-mediated suppression. In conclusion, tumor growth leads to a change in immunoregulation that causes suppression of the immune response."],"dc:description.degree":["Ph. D."],"dc:format.medium":["BTD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["etd-07122007-103932"],"dc:identifier.uri":["http://hdl.handle.net/10919/38779"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:title":["The association of tumor-induced changes in macrophage phenotype with immunosuppressive functions"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Microbiology and Immunology"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:02Z"}