Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice
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{"title"=>"Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Antonella", "last_name"=>"Montinaro", "scopus_author_id"=>"37054556000"}, {"first_name"=>"Giovanni", "last_name"=>"Forte", "scopus_author_id"=>"35069130000"}, {"first_name"=>"Rosalinda", "last_name"=>"Sorrentino", "scopus_author_id"=>"14065472200"}, {"first_name"=>"Antonio", "last_name"=>"Luciano", "scopus_author_id"=>"36637763600"}, {"first_name"=>"Giuseppe", "last_name"=>"Palma", "scopus_author_id"=>"27467758800"}, {"first_name"=>"Claudio", "last_name"=>"Arra", "scopus_author_id"=>"6603289350"}, {"first_name"=>"Ian M.", "last_name"=>"Adcock", "scopus_author_id"=>"7007066538"}, {"first_name"=>"Aldo", "last_name"=>"Pinto", "scopus_author_id"=>"7402306499"}, {"first_name"=>"Silvana", "last_name"=>"Morello", "scopus_author_id"=>"6602467436"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"84866719355", "scopus"=>"2-s2.0-84866719355", "pui"=>"365720476", "doi"=>"10.1371/journal.pone.0045401", "pmid"=>"23028986"}, "id"=>"589fa4a3-dc2f-31c9-b291-aa08be3d7442", "abstract"=>"Cl-IB-MECA is a selective A3 adenosine receptor agonist, which plays a crucial role in limiting tumor progression. In mice, Cl-IB-MECA administration enhances the anti-tumor T cell-mediated response. However, little is known about the activity of Cl-IB-MECA on CD8+ T cells. The aim of this study was to investigate the effect of ex vivo Cl-IB-MECA treatment of CD8+ T cells, adoptively transferred in melanoma-bearing mice. Adoptive transfer of Cl-IB-MECA-treated CD8+ T cells or a single administration of Cl-IB-MECA (20 ng/mouse) inhibited tumor growth compared with the control group and significantly improved mouse survival. This was associated with the release of Th1-type cytokines and a greater influx of mature Langerin+ dendritic cells (LCs) into the tumor microenvironment. CD8+ T cells treated with Cl-IB-MECA released TNF-α which plays a critical role in the therapeutic efficacy of these cells when injected to mice. Indeed, neutralization of TNF-α by a specific monoclonal Ab significantly blocked the anti-tumor activity of Cl-IB-MECA-treated T cells. This was due to the reduction in levels of cytotoxic cytokines and the presence of fewer LCs. In conclusion, these studies reveal that ex vivo treatment with Cl-IB-MECA improves CD8+ T cell adoptive immunotherapy for melanoma in a TNF-α-dependent manner.", "link"=>"http://www.mendeley.com/research/adoptive-immunotherapy-clibmecatreated-cd8-t-cells-reduces-melanoma-growth-mice-1", "reader_count"=>6, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/570353"], "description"=>"<p><b>A</b>) and <b>B</b>) TNF-α and granzyme B levels, respectively, detected into tissue homogenates from mice adoptively transferred with Cl-IB-MECA-stimulated CD8+ T cells or Cl-IB-MECA-treated mice. <b>C</b>) Representative pictures of melanoma cryosections Tunel stained (FITC) and stained with PI (red). Positive and negative controls are also provided. <b>D</b>) Quantitative analysis of Tunel+ cells detected in melanoma sections. Results are expressed as mean ± SEM (n = 5/group). Data are from two independent experiments and represent mean ± SEM, n = 6 in each experiment. Statistical difference was determined by one way ANOVA. *p<0.05, **p<0.01, ***p<0.001.</p>", "links"=>[], "tags"=>["cl-ib-meca", "apoptosis", "granzyme", "melanoma"], "article_id"=>240832, "categories"=>["Cancer", "Immunology"], "users"=>["Antonella Montinaro", "Giovanni Forte", "Rosalinda Sorrentino", "Antonio Luciano", "Giuseppe Palma", "Claudio Arra", "Ian M. Adcock", "Aldo Pinto", "Silvana Morello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045401.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_effectiveness_of_CD8_T_cell_transfer_after_Cl_IB_MECA_treatment_is_associated_with_increased_apoptosis_rate_granzyme_B_and_TNF_release_into_melanoma_lesions_/240832", "title"=>"<i>In vivo</i> effectiveness of CD8+ T cell transfer after Cl-IB-MECA treatment is associated with increased apoptosis rate, granzyme B and TNF-α release into melanoma lesions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-24 00:13:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/303282", "https://ndownloader.figshare.com/files/303321", "https://ndownloader.figshare.com/files/303379", "https://ndownloader.figshare.com/files/303416"], "description"=>"<div><p>Cl-IB-MECA is a selective A3 adenosine receptor agonist, which plays a crucial role in limiting tumor progression. In mice, Cl-IB-MECA administration enhances the anti-tumor T cell-mediated response. However, little is known about the activity of Cl-IB-MECA on CD8+ T cells. The aim of this study was to investigate the effect of ex vivo Cl-IB-MECA treatment of CD8+ T cells, adoptively transferred in melanoma-bearing mice. Adoptive transfer of Cl-IB-MECA-treated CD8+ T cells or a single administration of Cl-IB-MECA (20 ng/mouse) inhibited tumor growth compared with the control group and significantly improved mouse survival. This was associated with the release of Th1-type cytokines and a greater influx of mature Langerin+ dendritic cells (LCs) into the tumor microenvironment. CD8+ T cells treated with Cl-IB-MECA released TNF-α which plays a critical role in the therapeutic efficacy of these cells when injected to mice. Indeed, neutralization of TNF-α by a specific monoclonal Ab significantly blocked the anti-tumor activity of Cl-IB-MECA-treated T cells. This was due to the reduction in levels of cytotoxic cytokines and the presence of fewer LCs. In conclusion, these studies reveal that ex vivo treatment with Cl-IB-MECA improves CD8+ T cell adoptive immunotherapy for melanoma in a TNF-α-dependent manner.</p> </div>", "links"=>[], "tags"=>["adoptive", "immunotherapy", "cl-ib-meca-treated", "cells", "reduces", "melanoma", "mice"], "article_id"=>119806, "categories"=>["Cancer", "Immunology"], "users"=>["Antonella Montinaro", "Giovanni Forte", "Rosalinda Sorrentino", "Antonio Luciano", "Giuseppe Palma", "Claudio Arra", "Ian M. Adcock", "Aldo Pinto", "Silvana Morello"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045401.s001", "https://dx.doi.org/10.1371/journal.pone.0045401.s002", "https://dx.doi.org/10.1371/journal.pone.0045401.s003", "https://dx.doi.org/10.1371/journal.pone.0045401.s004"], "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Adoptive_Immunotherapy_with_Cl_IB_MECA_Treated_CD8_T_Cells_Reduces_Melanoma_Growth_in_Mice/119806", "title"=>"Adoptive Immunotherapy with Cl-IB-MECA-Treated CD8+ T Cells Reduces Melanoma Growth in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-24 02:43:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/570267"], "description"=>"<p><b>A</b>) C57Bl6j mice were s.c. inoculated with 2.5×10<sup>5</sup>cells B16-F10 cells/mouse. 10 days after B16 injection, mice received a single p.t. injection of Cl-IB-MECA (20 ng/mouse) or 1×10<sup>6</sup> CD8+ T cells/mouse treated with Cl-IB-MECA (0.1 µg/ml) or 1×10<sup>6</sup> untreated CD8+ T cells/mouse or PBS (Ctr). <b>B</b>) Tumor volume (mm<sup>3</sup>) measured in control mice (Ctr, n = 11) and mice receiving a single dose of Cl-IB-MECA (n = 13) or adoptively transferred with Cl-IB-MECA-treated CD8+ T cells (n = 14) or with untreated CD8+ T cell (n = 10). <b>C</b>) Increased survival of melanoma-bearing mice receiving Cl-IB-MECA (p<0.05) or CD8+ T cell transfer cultured with Cl-IB-MECA (p<0.001) compared with control groups (n = 5/group). Data are from three independent experiments and represent mean ± SEM. Statistical differences were determined by one way ANOVA and Student's t test, as appropriate. ***p<0.001. Comparison of survival between groups was performed using long-rank test.</p>", "links"=>[], "tags"=>["cells", "cultured", "cl-ib-meca", "mediates", "enhanced", "suppression", "melanoma-bearing"], "article_id"=>240731, "categories"=>["Cancer", "Immunology"], "users"=>["Antonella Montinaro", "Giovanni Forte", "Rosalinda Sorrentino", "Antonio Luciano", "Giuseppe Palma", "Claudio Arra", "Ian M. Adcock", "Aldo Pinto", "Silvana Morello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045401.g001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adoptive_transfer_of_CD8_T_cells_cultured_with_Cl_IB_MECA_mediates_enhanced_tumor_suppression_in_melanoma_bearing_mice_/240731", "title"=>"Adoptive transfer of CD8+ T cells cultured with Cl-IB-MECA mediates enhanced tumor suppression in melanoma-bearing mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-24 00:12:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/570446"], "description"=>"<p><b>A</b>) Tumor volume (mm<sup>3</sup>) measured in melanoma-bearing Nude mice receiving a single dose of Cl-IB-MECA or adoptively transferred with Cl-IB-MECA-treated CD8+ T cells or with untreated CD8+ T cells. <b>B</b>) Increased survival of melanoma-bearing Nude mice receiving CD8+ T cell transfer, cultured with Cl-IB-MECA (p<0.01) compared with control groups and Cl-IB-MECA-treated mice (n = 5/group). Data represent mean ± SEM, n = 6 in each of two independent experiments. Statistical difference was determined by one way ANOVA. *p<0.05. Comparison of survival between groups was performed using long-rank test.</p>", "links"=>[], "tags"=>["inhibited", "nude", "mice", "adoptively", "transferred", "cells", "stimulated"], "article_id"=>240917, "categories"=>["Cancer", "Immunology"], "users"=>["Antonella Montinaro", "Giovanni Forte", "Rosalinda Sorrentino", "Antonio Luciano", "Giuseppe Palma", "Claudio Arra", "Ian M. Adcock", "Aldo Pinto", "Silvana Morello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045401.g003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumor_growth_is_inhibited_in_Nude_mice_adoptively_transferred_with_CD8_T_cells_stimulated_with_Cl_IB_MECA_/240917", "title"=>"Tumor growth is inhibited in Nude mice adoptively transferred with CD8+ T cells stimulated with Cl-IB-MECA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-24 00:15:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/570531"], "description"=>"<p><b>A</b>) A3 adenosine receptor expression by CD8+ T cells. <b>B</b>) TNF-α levels in the supernatants of naïve (white bars) and activated (black bars) CD8+ T cells after Cl-IB-MECA treatment measured at 24 h by ELISA. <b>C</b>) INF-γ production measured in the supernatants of naïve (white bars) and activated (black bars) CD8+ T cells stimulated or not with Cl-IB-MECA (0.1 µg/ml) and measured at 72 h by means of ELISA. . <b>D</b>), <b>E</b>) and <b>F</b>) percentage of CD69+ cells, CD25+ cells or CD27+ cells, respectively, after Cl-IB-MECA treatment. <b>G</b>) MRS1191 blocked the stimulatory effect of Cl-IB-MECA on TNF-α release. Data are from two independent experiments and represent mean ± SEM, n = 8 for each experiment. Statistical difference was determined by Student's <i>t</i> test. *p<0.05.</p>", "links"=>[], "tags"=>["stimulation", "cells", "favors"], "article_id"=>241012, "categories"=>["Cancer", "Immunology"], "users"=>["Antonella Montinaro", "Giovanni Forte", "Rosalinda Sorrentino", "Antonio Luciano", "Giuseppe Palma", "Claudio Arra", "Ian M. Adcock", "Aldo Pinto", "Silvana Morello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045401.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cl_IB_MECA_stimulation_of_CD8_T_cells_in_vitro_favors_TNF_production_/241012", "title"=>"Cl-IB-MECA stimulation of CD8+ T cells <i>in vitro</i> favors TNF-α production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-24 00:16:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/570621"], "description"=>"<p><b>A</b>) Tumor volume (mm3) in mice receiving anti-TNF-α mAb (dashed lines) or isotype IgG control (continuous lines) and injected with Cl-IB-MECA or PBS or CD8+ T cells treated or not with Cl-IB-MECA. <b>B</b>) Percentage of CD11c+CD207 high cells in the tissue of mice described above. <b>C</b>) Representative dot plot is shown. <b>D</b>) and <b>E</b>) Expression of CD80 and MHC I, respectively, on CD11c+CD207 high cells in the tissue of mice described above. Data are from two independent experiments and represent mean ± SEM, n = 9 for each experiment. Statistical difference was determined by one way ANOVA. *p<0.05, **p<0.01, ***p<0.001.</p>", "links"=>[], "tags"=>["abrogated", "anti-tumor", "cl-ib-meca-treated"], "article_id"=>241104, "categories"=>["Cancer", "Immunology"], "users"=>["Antonella Montinaro", "Giovanni Forte", "Rosalinda Sorrentino", "Antonio Luciano", "Giuseppe Palma", "Claudio Arra", "Ian M. Adcock", "Aldo Pinto", "Silvana Morello"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045401.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_of_TNF_945_abrogated_the_anti_tumor_effect_of_Cl_IB_MECA_treated_CD8_T_cells_/241104", "title"=>"Neutralization of TNF-α abrogated the anti-tumor effect of Cl-IB-MECA-treated CD8+ T cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-24 00:18:24"}

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Relative Metric

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