Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines
Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL...
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| Veröffentlicht in: | Journal of clinical immunology 2004-01, Vol.24 (1), p.86-96 |
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| creator | Arroyo, J Carlos Gabilondo, Fernando Llorente, Luis Meraz-Ríos, Marco A Sánchez-Torres, Carmen |
| description | Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14(high)CD16(-) monocytes (16-mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16-mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-gamma/IL-4 ratio against TuLy and KLH was higher when using 16-mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16-mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo. |
| doi_str_mv | 10.1023/B:JOCI.0000018067.71622.fb |
| format | Article |
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However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14(high)CD16(-) monocytes (16-mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16-mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-gamma/IL-4 ratio against TuLy and KLH was higher when using 16-mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16-mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo.</description><identifier>ISSN: 0271-9142</identifier><identifier>EISSN: 1573-2592</identifier><identifier>DOI: 10.1023/B:JOCI.0000018067.71622.fb</identifier><identifier>PMID: 14997038</identifier><identifier>CODEN: JCIMDO</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Adolescent ; Adult ; Antigens, Neoplasm - immunology ; Cancer Vaccines - immunology ; Cancer Vaccines - therapeutic use ; Carcinoma, Renal Cell - immunology ; Carcinoma, Renal Cell - pathology ; Carcinoma, Renal Cell - therapy ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell Division - immunology ; Cytokines - immunology ; Cytokines - metabolism ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Dendritic Cells - transplantation ; Hemocyanins - immunology ; Humans ; Hypersensitivity, Delayed - immunology ; Immunoglobulin G - immunology ; Immunoglobulin Isotypes - immunology ; Immunotherapy ; Kidney Neoplasms - immunology ; Kidney Neoplasms - pathology ; Kidney Neoplasms - therapy ; Lung Neoplasms - immunology ; Lung Neoplasms - secondary ; Lung Neoplasms - therapy ; Male ; Middle Aged ; Nephrectomy ; Receptors, IgG - immunology</subject><ispartof>Journal of clinical immunology, 2004-01, Vol.24 (1), p.86-96</ispartof><rights>Plenum Publishing Corporation 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c342t-90acc72e5854210b42c52b2d79b6492439165b676a41efd2ab662121e2ffa2243</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14997038$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arroyo, J Carlos</creatorcontrib><creatorcontrib>Gabilondo, Fernando</creatorcontrib><creatorcontrib>Llorente, Luis</creatorcontrib><creatorcontrib>Meraz-Ríos, Marco A</creatorcontrib><creatorcontrib>Sánchez-Torres, Carmen</creatorcontrib><title>Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines</title><title>Journal of clinical immunology</title><addtitle>J Clin Immunol</addtitle><description>Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14(high)CD16(-) monocytes (16-mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16-mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-gamma/IL-4 ratio against TuLy and KLH was higher when using 16-mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16-mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Carcinoma, Renal Cell - immunology</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Carcinoma, Renal Cell - therapy</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell Division - immunology</subject><subject>Cytokines - immunology</subject><subject>Cytokines - metabolism</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - pathology</subject><subject>Dendritic Cells - transplantation</subject><subject>Hemocyanins - immunology</subject><subject>Humans</subject><subject>Hypersensitivity, Delayed - immunology</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin Isotypes - immunology</subject><subject>Immunotherapy</subject><subject>Kidney Neoplasms - immunology</subject><subject>Kidney Neoplasms - pathology</subject><subject>Kidney Neoplasms - therapy</subject><subject>Lung Neoplasms - immunology</subject><subject>Lung Neoplasms - secondary</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nephrectomy</subject><subject>Receptors, IgG - immunology</subject><issn>0271-9142</issn><issn>1573-2592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkU1v1DAQhi0EokvhLyCrBy4oiz1J7KQ3unwtqtQLnC1_TISrjbPYzlb7l_iVONuVKvBlLPl5Z8Z6CLnibM0Z1B9urr_fbbZrthzeMSHXkguA9WCekRVvZV1B28NzsmIgedXzBi7Iq5TuC14LaF-SC970vWR1tyJ_tuM4B6QR034KCakPbrboSqUHn-NEzZFuPnFRUR3c6faejlOY7DFj5TD6Q4EdBhd99pZa3O3SEt7r7DHkRB98_kVHzDplvRARg96dOGp1tD5Mo6Y5os6l0Qn-txs9aFsoTK_Ji0HvEr4510vy88vnH5tv1e3d1-3m421l6wZy1bPCS8C2axvgzDRgWzDgZG9E00NT91y0RkihG46DA22EAA4cYRg0lPdL8u6x7z5Ov2dMWY0-LZvogNOclOSyaOi6Al79B95Pcyy_Swq46HpRRhXo-hGycUop4qD20Y86HhVnatGpbtSiUz3pVCedajAl_PY8YTYjuqfo2V_9F0p-nbA</recordid><startdate>200401</startdate><enddate>200401</enddate><creator>Arroyo, J Carlos</creator><creator>Gabilondo, Fernando</creator><creator>Llorente, Luis</creator><creator>Meraz-Ríos, Marco A</creator><creator>Sánchez-Torres, Carmen</creator><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200401</creationdate><title>Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines</title><author>Arroyo, J Carlos ; Gabilondo, Fernando ; Llorente, Luis ; Meraz-Ríos, Marco A ; Sánchez-Torres, Carmen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c342t-90acc72e5854210b42c52b2d79b6492439165b676a41efd2ab662121e2ffa2243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antigens, Neoplasm - 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therapy</topic><topic>Lung Neoplasms - immunology</topic><topic>Lung Neoplasms - secondary</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nephrectomy</topic><topic>Receptors, IgG - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arroyo, J Carlos</creatorcontrib><creatorcontrib>Gabilondo, Fernando</creatorcontrib><creatorcontrib>Llorente, Luis</creatorcontrib><creatorcontrib>Meraz-Ríos, Marco A</creatorcontrib><creatorcontrib>Sánchez-Torres, Carmen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science 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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arroyo, J Carlos</au><au>Gabilondo, Fernando</au><au>Llorente, Luis</au><au>Meraz-Ríos, Marco A</au><au>Sánchez-Torres, Carmen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines</atitle><jtitle>Journal of clinical immunology</jtitle><addtitle>J Clin Immunol</addtitle><date>2004-01</date><risdate>2004</risdate><volume>24</volume><issue>1</issue><spage>86</spage><epage>96</epage><pages>86-96</pages><issn>0271-9142</issn><eissn>1573-2592</eissn><coden>JCIMDO</coden><abstract>Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14(high)CD16(-) monocytes (16-mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16-mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-gamma/IL-4 ratio against TuLy and KLH was higher when using 16-mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16-mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo.</abstract><cop>Netherlands</cop><pub>Springer Nature B.V</pub><pmid>14997038</pmid><doi>10.1023/B:JOCI.0000018067.71622.fb</doi><tpages>11</tpages></addata></record> |
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| subjects | Adolescent Adult Antigens, Neoplasm - immunology Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Carcinoma, Renal Cell - immunology Carcinoma, Renal Cell - pathology Carcinoma, Renal Cell - therapy CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Division - immunology Cytokines - immunology Cytokines - metabolism Dendritic Cells - immunology Dendritic Cells - pathology Dendritic Cells - transplantation Hemocyanins - immunology Humans Hypersensitivity, Delayed - immunology Immunoglobulin G - immunology Immunoglobulin Isotypes - immunology Immunotherapy Kidney Neoplasms - immunology Kidney Neoplasms - pathology Kidney Neoplasms - therapy Lung Neoplasms - immunology Lung Neoplasms - secondary Lung Neoplasms - therapy Male Middle Aged Nephrectomy Receptors, IgG - immunology |
| title | Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines |
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