Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice
Subclinical doses of Paclitaxel (PTX) given 1 day prior to a HER-2/ neu (neu)-targeted, granulocyte–macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu + tumor growth in tolerized HER-2/ neu ( neu-N) mice. We demonstrate tha...
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| Veröffentlicht in: | Cellular immunology 2010, Vol.263 (1), p.79-87 |
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| creator | Pfannenstiel, Lukas W. Lam, Samuel S.K. Emens, Leisha A. Jaffee, Elizabeth M. Armstrong, Todd D. |
| description | Subclinical doses of Paclitaxel (PTX) given 1
day prior to a HER-2/
neu (neu)-targeted, granulocyte–macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu
+ tumor growth in tolerized HER-2/
neu (
neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that
in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8
+ T cells with enhanced lytic activity against neu
+ tumors. PTX treatment also enhances maturation marker expression on CD11c
+ DCs isolated from vaccine-draining lymph nodes.
Ex vivo, these DCs activate CD8
+ T cells with greater lytic capability than DC’s from vaccine alone-treated
neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-γ-secreting CD8
+ T cells
in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC. |
| doi_str_mv | 10.1016/j.cellimm.2010.03.001 |
| format | Article |
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day prior to a HER-2/
neu (neu)-targeted, granulocyte–macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu
+ tumor growth in tolerized HER-2/
neu (
neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that
in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8
+ T cells with enhanced lytic activity against neu
+ tumors. PTX treatment also enhances maturation marker expression on CD11c
+ DCs isolated from vaccine-draining lymph nodes.
Ex vivo, these DCs activate CD8
+ T cells with greater lytic capability than DC’s from vaccine alone-treated
neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-γ-secreting CD8
+ T cells
in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC.</description><identifier>ISSN: 0008-8749</identifier><identifier>EISSN: 1090-2163</identifier><identifier>DOI: 10.1016/j.cellimm.2010.03.001</identifier><identifier>PMID: 20346445</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Antigens, CD - biosynthesis ; Antigens, Neoplasm - immunology ; Cancer Vaccines ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; Cell Differentiation - drug effects ; Cell Line, Tumor ; Chemotherapy, Adjuvant ; Combination therapy ; Cross-presentation ; Cyclophosphamide ; Cyclophosphamide - administration & dosage ; Cyclophosphamide - pharmacology ; Cytokines - genetics ; Cytokines - metabolism ; Cytotoxicity, Immunologic - drug effects ; Dendritic cell ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dendritic Cells - pathology ; Drug Therapy, Combination ; Granulocyte-Macrophage Colony-Stimulating Factor - immunology ; Immunomodulation ; Immunotherapy ; Lymphocyte Activation - drug effects ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Neoplasms - immunology ; Neoplasms - therapy ; Paclitaxel ; Paclitaxel - pharmacology ; Receptor, ErbB-2 - immunology ; Signal Transduction - drug effects ; Toll-Like Receptor 4 - metabolism ; Tumor Burden - drug effects</subject><ispartof>Cellular immunology, 2010, Vol.263 (1), p.79-87</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-bc30c173ca702ceada5f92111a8e0590dc86b77cf786d6bfe90c391250d33c4f3</citedby><cites>FETCH-LOGICAL-c498t-bc30c173ca702ceada5f92111a8e0590dc86b77cf786d6bfe90c391250d33c4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cellimm.2010.03.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,4010,27904,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20346445$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pfannenstiel, Lukas W.</creatorcontrib><creatorcontrib>Lam, Samuel S.K.</creatorcontrib><creatorcontrib>Emens, Leisha A.</creatorcontrib><creatorcontrib>Jaffee, Elizabeth M.</creatorcontrib><creatorcontrib>Armstrong, Todd D.</creatorcontrib><title>Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice</title><title>Cellular immunology</title><addtitle>Cell Immunol</addtitle><description>Subclinical doses of Paclitaxel (PTX) given 1
day prior to a HER-2/
neu (neu)-targeted, granulocyte–macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu
+ tumor growth in tolerized HER-2/
neu (
neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that
in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8
+ T cells with enhanced lytic activity against neu
+ tumors. PTX treatment also enhances maturation marker expression on CD11c
+ DCs isolated from vaccine-draining lymph nodes.
Ex vivo, these DCs activate CD8
+ T cells with greater lytic capability than DC’s from vaccine alone-treated
neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-γ-secreting CD8
+ T cells
in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC.</description><subject>Animals</subject><subject>Antigens, CD - biosynthesis</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Cancer Vaccines</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy, Adjuvant</subject><subject>Combination therapy</subject><subject>Cross-presentation</subject><subject>Cyclophosphamide</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Cyclophosphamide - pharmacology</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Cytotoxicity, Immunologic - drug effects</subject><subject>Dendritic cell</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - pathology</subject><subject>Drug Therapy, Combination</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - immunology</subject><subject>Immunomodulation</subject><subject>Immunotherapy</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - therapy</subject><subject>Paclitaxel</subject><subject>Paclitaxel - pharmacology</subject><subject>Receptor, ErbB-2 - immunology</subject><subject>Signal Transduction - drug effects</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Tumor Burden - drug effects</subject><issn>0008-8749</issn><issn>1090-2163</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhJ4B845RlbOfDuYBQxZe0UlHVni3veLLrVeIU26naf0_CLhWcerLGfuZ9PfMy9lbAWoCoPxzWSH3vh2EtYb4DtQYQz9hKQAuFFLV6zlYAoAvdlO0Ze5XSYQZE2cJLdiZBlXVZVitmflrsfbb31HMKexuQEicb-wfuKLjos0e-OPHB5ina7MfAbXC8mwL-KfI-jtNuz683VyVPfhds78OO-8AHj_Savehsn-jN6TxnN1-_XF98LzaX335cfN4UWLY6F1tUgKJRaBuQSNbZqmulEMJqgqoFh7reNg12ja5dve2oBVStkBU4pbDs1Dn7eNS9nbYDOaSQo-3NbfSDjQ9mtN78_xL83uzGOyN1LbWCWeD9SSCOvyZK2Qw-LYPbQOOUjBZVpWQjF7I6khjHlCJ1jy4CzJKNOZhTNmbJxoAy8-rnvnf_fvGx628YM_DpCNC8qDtP0ST0NCfifCTMxo3-CYvfQVGlHw</recordid><startdate>2010</startdate><enddate>2010</enddate><creator>Pfannenstiel, Lukas W.</creator><creator>Lam, Samuel S.K.</creator><creator>Emens, Leisha A.</creator><creator>Jaffee, Elizabeth M.</creator><creator>Armstrong, Todd D.</creator><general>Elsevier Inc</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>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>2010</creationdate><title>Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice</title><author>Pfannenstiel, Lukas W. ; Lam, Samuel S.K. ; Emens, Leisha A. ; Jaffee, Elizabeth M. ; Armstrong, Todd D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-bc30c173ca702ceada5f92111a8e0590dc86b77cf786d6bfe90c391250d33c4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antigens, CD - biosynthesis</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Cancer Vaccines</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy, Adjuvant</topic><topic>Combination therapy</topic><topic>Cross-presentation</topic><topic>Cyclophosphamide</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Cyclophosphamide - pharmacology</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Cytotoxicity, Immunologic - drug effects</topic><topic>Dendritic cell</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Dendritic Cells - pathology</topic><topic>Drug Therapy, Combination</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - immunology</topic><topic>Immunomodulation</topic><topic>Immunotherapy</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neoplasm Transplantation</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - therapy</topic><topic>Paclitaxel</topic><topic>Paclitaxel - pharmacology</topic><topic>Receptor, ErbB-2 - immunology</topic><topic>Signal Transduction - drug effects</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Tumor Burden - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pfannenstiel, Lukas W.</creatorcontrib><creatorcontrib>Lam, Samuel S.K.</creatorcontrib><creatorcontrib>Emens, Leisha A.</creatorcontrib><creatorcontrib>Jaffee, Elizabeth M.</creatorcontrib><creatorcontrib>Armstrong, Todd D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pfannenstiel, Lukas W.</au><au>Lam, Samuel S.K.</au><au>Emens, Leisha A.</au><au>Jaffee, Elizabeth M.</au><au>Armstrong, Todd D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice</atitle><jtitle>Cellular immunology</jtitle><addtitle>Cell Immunol</addtitle><date>2010</date><risdate>2010</risdate><volume>263</volume><issue>1</issue><spage>79</spage><epage>87</epage><pages>79-87</pages><issn>0008-8749</issn><eissn>1090-2163</eissn><abstract>Subclinical doses of Paclitaxel (PTX) given 1
day prior to a HER-2/
neu (neu)-targeted, granulocyte–macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu
+ tumor growth in tolerized HER-2/
neu (
neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that
in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8
+ T cells with enhanced lytic activity against neu
+ tumors. PTX treatment also enhances maturation marker expression on CD11c
+ DCs isolated from vaccine-draining lymph nodes.
Ex vivo, these DCs activate CD8
+ T cells with greater lytic capability than DC’s from vaccine alone-treated
neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-γ-secreting CD8
+ T cells
in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>20346445</pmid><doi>10.1016/j.cellimm.2010.03.001</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-8749 |
| ispartof | Cellular immunology, 2010, Vol.263 (1), p.79-87 |
| issn | 0008-8749 1090-2163 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2862830 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antigens, CD - biosynthesis Antigens, Neoplasm - immunology Cancer Vaccines CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Cell Differentiation - drug effects Cell Line, Tumor Chemotherapy, Adjuvant Combination therapy Cross-presentation Cyclophosphamide Cyclophosphamide - administration & dosage Cyclophosphamide - pharmacology Cytokines - genetics Cytokines - metabolism Cytotoxicity, Immunologic - drug effects Dendritic cell Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Dendritic Cells - pathology Drug Therapy, Combination Granulocyte-Macrophage Colony-Stimulating Factor - immunology Immunomodulation Immunotherapy Lymphocyte Activation - drug effects Mice Mice, Transgenic Neoplasm Transplantation Neoplasms - immunology Neoplasms - therapy Paclitaxel Paclitaxel - pharmacology Receptor, ErbB-2 - immunology Signal Transduction - drug effects Toll-Like Receptor 4 - metabolism Tumor Burden - drug effects |
| title | Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice |
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