A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy
A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tum...
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| Veröffentlicht in: | PloS one 2014-08, Vol.9 (8), p.e104351-e104351 |
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| creator | Lee, Seung Jun Shin, Sung Jae Lee, Moon Hee Lee, Min-Goo Kang, Tae Heung Park, Won Sun Soh, Byoung Yul Park, Jung Hee Shin, Yong Kyoo Kim, Han Wool Yun, Cheol-Heui Jung, In Duk Park, Yeong-Min |
| description | A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy. |
| doi_str_mv | 10.1371/journal.pone.0104351 |
| format | Article |
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The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0104351</identifier><identifier>PMID: 25102137</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptor Proteins, Vesicular Transport - genetics ; Adaptor Proteins, Vesicular Transport - immunology ; Adjuvants, Immunologic - chemistry ; Adjuvants, Immunologic - pharmacology ; Agricultural biotechnology ; Agriculture ; Animals ; Antigens ; Bacterial Proteins - chemistry ; Bacterial Proteins - pharmacology ; Biology and Life Sciences ; Cancer ; CD4 antigen ; CD8 antigen ; Cell Line, Tumor ; Cell survival ; Cell-mediated immunity ; Cytokines - genetics ; Cytokines - immunology ; Cytotoxicity ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Drug therapy ; Effector cells ; Immune system ; Immunity ; Immunity, Cellular - genetics ; Immunity, Cellular - immunology ; Immunization ; Immunology ; Immunotherapy ; Inflammation ; Interferon ; Interleukin 1 ; Interleukin 6 ; Life sciences ; Ligands ; Lymphocytes ; Lymphocytes T ; Maturation ; Medicine ; Medicine and Health Sciences ; Mice, Knockout ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - chemistry ; MyD88 protein ; Neoplasms, Experimental - immunology ; Neoplasms, Experimental - pathology ; Neoplasms, Experimental - therapy ; Ovalbumin ; Phenotypes ; Physiology ; Proteins ; Ribosomal protein L7 ; Signaling ; Survival ; T cell receptors ; T cells ; Thymoma ; TLR4 protein ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 4 - immunology ; Toll-like receptors ; Toxicity ; Tuberculosis ; Tumor necrosis factor ; Tumor necrosis factor-α ; Tumors ; Vaccines</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e104351-e104351</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Lee et al 2014 Lee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-90e408b2d96d7caa5eedb12d1cec9219b05195291b8dc13d8c1d695e0ce885ca3</citedby><cites>FETCH-LOGICAL-c692t-90e408b2d96d7caa5eedb12d1cec9219b05195291b8dc13d8c1d695e0ce885ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125215/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125215/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25102137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Seung Jun</creatorcontrib><creatorcontrib>Shin, Sung Jae</creatorcontrib><creatorcontrib>Lee, Moon Hee</creatorcontrib><creatorcontrib>Lee, Min-Goo</creatorcontrib><creatorcontrib>Kang, Tae Heung</creatorcontrib><creatorcontrib>Park, Won Sun</creatorcontrib><creatorcontrib>Soh, Byoung Yul</creatorcontrib><creatorcontrib>Park, Jung Hee</creatorcontrib><creatorcontrib>Shin, Yong Kyoo</creatorcontrib><creatorcontrib>Kim, Han Wool</creatorcontrib><creatorcontrib>Yun, Cheol-Heui</creatorcontrib><creatorcontrib>Jung, In Duk</creatorcontrib><creatorcontrib>Park, Yeong-Min</creatorcontrib><title>A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.</description><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Adaptor Proteins, Vesicular Transport - immunology</subject><subject>Adjuvants, Immunologic - chemistry</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Agricultural biotechnology</subject><subject>Agriculture</subject><subject>Animals</subject><subject>Antigens</subject><subject>Bacterial Proteins - chemistry</subject><subject>Bacterial Proteins - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cell survival</subject><subject>Cell-mediated immunity</subject><subject>Cytokines - genetics</subject><subject>Cytokines - 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immunology</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Neoplasms, Experimental - therapy</subject><subject>Ovalbumin</subject><subject>Phenotypes</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Ribosomal protein L7</subject><subject>Signaling</subject><subject>Survival</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>Thymoma</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - genetics</subject><subject>Toll-Like Receptor 4 - immunology</subject><subject>Toll-like receptors</subject><subject>Toxicity</subject><subject>Tuberculosis</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-α</subject><subject>Tumors</subject><subject>Vaccines</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0uP0zAUhSMEYoaBf4AgEhKCRYuvE-exQapGPCoNGml4bC3Hvm1dJXawnYpu-O24NDNq0CxQFrFuvnPse-KbJM-BzCEr4d3WDs6Idt5bg3MCJM8YPEjOoc7orKAke3iyPkueeL8lhGVVUTxOzigDQqPLefJ7kfY2oAlatGnv4lKbVKjtsBMmpAqd3qFKV8526Ze9tI2QIdaGLg1Dg04OrfXapzc7UjCaotkII9FHnVFOBy1TiW3rZ43w0SUMnXWp7rrB2LBBJ_r90-TRSrQen43vi-T7xw_fLj_Prq4_LS8XVzNZ1DTMaoI5qRqq6kKVUgiGqBqgCiTKmkLdEAY1ozU0lZKQqUqCKmqGRGJVMSmyi-Tl0bePB-ZjdJ5TAjkpIacsEssjoazY8t7pTrg9t0LzvwXr1ly42FGLvGloWZEYK64gZ5TWWZYDIZDJXCGVdfR6P-42NB0qGeN1op2YTr8YveFru-M5UEbhcJg3o4GzPwf0gXfaH6IUBu3gOTBG4x0oiyqir_5B7-9upNYiNqDNysZ95cGUL3KoSlKxkkZqfg8VH4WdlvGerXSsTwRvJ4LIBPwV1mLwni-_3vw_e_1jyr4-YTco2rDxth2CtsZPwfwISme9d7i6CxkIP4zJbRr8MCZ8HJMoe3H6g-5Et3OR_QEkqQ5Q</recordid><startdate>20140807</startdate><enddate>20140807</enddate><creator>Lee, Seung Jun</creator><creator>Shin, Sung Jae</creator><creator>Lee, Moon Hee</creator><creator>Lee, Min-Goo</creator><creator>Kang, Tae Heung</creator><creator>Park, Won Sun</creator><creator>Soh, Byoung Yul</creator><creator>Park, Jung Hee</creator><creator>Shin, Yong Kyoo</creator><creator>Kim, Han Wool</creator><creator>Yun, Cheol-Heui</creator><creator>Jung, In Duk</creator><creator>Park, Yeong-Min</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140807</creationdate><title>A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy</title><author>Lee, Seung Jun ; Shin, Sung Jae ; Lee, Moon Hee ; Lee, Min-Goo ; Kang, Tae Heung ; Park, Won Sun ; Soh, Byoung Yul ; Park, Jung Hee ; Shin, Yong Kyoo ; Kim, Han Wool ; Yun, Cheol-Heui ; Jung, In Duk ; Park, Yeong-Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-90e408b2d96d7caa5eedb12d1cec9219b05195291b8dc13d8c1d695e0ce885ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Vesicular Transport - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Seung Jun</au><au>Shin, Sung Jae</au><au>Lee, Moon Hee</au><au>Lee, Min-Goo</au><au>Kang, Tae Heung</au><au>Park, Won Sun</au><au>Soh, Byoung Yul</au><au>Park, Jung Hee</au><au>Shin, Yong Kyoo</au><au>Kim, Han Wool</au><au>Yun, Cheol-Heui</au><au>Jung, In Duk</au><au>Park, Yeong-Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-07</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e104351</spage><epage>e104351</epage><pages>e104351-e104351</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25102137</pmid><doi>10.1371/journal.pone.0104351</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-08, Vol.9 (8), p.e104351-e104351 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2014071425 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adaptor Proteins, Vesicular Transport - genetics Adaptor Proteins, Vesicular Transport - immunology Adjuvants, Immunologic - chemistry Adjuvants, Immunologic - pharmacology Agricultural biotechnology Agriculture Animals Antigens Bacterial Proteins - chemistry Bacterial Proteins - pharmacology Biology and Life Sciences Cancer CD4 antigen CD8 antigen Cell Line, Tumor Cell survival Cell-mediated immunity Cytokines - genetics Cytokines - immunology Cytotoxicity Dendritic cells Dendritic Cells - immunology Dendritic Cells - pathology Drug therapy Effector cells Immune system Immunity Immunity, Cellular - genetics Immunity, Cellular - immunology Immunization Immunology Immunotherapy Inflammation Interferon Interleukin 1 Interleukin 6 Life sciences Ligands Lymphocytes Lymphocytes T Maturation Medicine Medicine and Health Sciences Mice, Knockout Mycobacterium tuberculosis Mycobacterium tuberculosis - chemistry MyD88 protein Neoplasms, Experimental - immunology Neoplasms, Experimental - pathology Neoplasms, Experimental - therapy Ovalbumin Phenotypes Physiology Proteins Ribosomal protein L7 Signaling Survival T cell receptors T cells Thymoma TLR4 protein Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - immunology Toll-like receptors Toxicity Tuberculosis Tumor necrosis factor Tumor necrosis factor-α Tumors Vaccines |
| title | A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy |
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