Low Molecular Weight Hyaluronan-Pulsed Human Dendritic Cells Showed Increased Migration Capacity and Induced Resistance to Tumor Chemoattraction
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{"title"=>"Low molecular weight hyaluronan-pulsed human dendritic cells showed increased migration capacity and induced resistance to tumor chemoattraction", "type"=>"journal", "authors"=>[{"first_name"=>"Manglio", "last_name"=>"Rizzo", "scopus_author_id"=>"23010232100"}, {"first_name"=>"Juan", "last_name"=>"Bayo", "scopus_author_id"=>"23979263500"}, {"first_name"=>"Flavia", "last_name"=>"Piccioni", "scopus_author_id"=>"36187151800"}, {"first_name"=>"Mariana", "last_name"=>"Malvicini", "scopus_author_id"=>"26021919000"}, {"first_name"=>"Esteban", "last_name"=>"Fiore", "scopus_author_id"=>"53871399000"}, {"first_name"=>"Estanislao", "last_name"=>"Peixoto", "scopus_author_id"=>"19640691000"}, {"first_name"=>"Mariana G.", "last_name"=>"García", "scopus_author_id"=>"35586734900"}, {"first_name"=>"Jorge B.", "last_name"=>"Aquino", "scopus_author_id"=>"8586256600"}, {"first_name"=>"Ariel Gonzalez", "last_name"=>"Campaña", "scopus_author_id"=>"55293489700"}, {"first_name"=>"Gustavo", "last_name"=>"Podestá", "scopus_author_id"=>"23028807300"}, {"first_name"=>"Marcelo", "last_name"=>"Terres", "scopus_author_id"=>"39462298400"}, {"first_name"=>"Oscar", "last_name"=>"Andriani", "scopus_author_id"=>"23027121300"}, {"first_name"=>"Laura", "last_name"=>"Alaniz", "scopus_author_id"=>"6506916478"}, {"first_name"=>"Guillermo", "last_name"=>"Mazzolini", "scopus_author_id"=>"6701641412"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0107944", "issn"=>"19326203", "sgr"=>"84907200351", "scopus"=>"2-s2.0-84907200351", "pui"=>"600046281", "pmid"=>"25238610"}, "id"=>"b9b76457-aaaa-3b7f-a6cf-dd39ec1af71d", "abstract"=>"We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated the effects of LMW HA priming on human-tumor-pulsed monocytes-derived dendritic cells (DC/TL) obtained from healthy donors and patients with CRC. LMW HA treatment resulted in an improved maturation state of DC/TL and an enhanced mixed leucocyte reaction activity in vivo. Importantly, pre-conditioning of DC/TL with LMW HA increased their ability to migrate and reduced their attraction to human tumor derived supernatants. These effects were associated with increased CCR7 expression levels in DC. Indeed, a significant increase in migratory response toward CCL21 was observed in LMW HA primed tumor-pulsed monocyte-derived dendritic cells (DC/TL/LMW HA) when compared to LWM HA untreated cells (DC/TL). Moreover, LMW HA priming modulated other mechanisms implicated in DC migration toward lymph nodes such as the metalloproteinase activity. Furthermore, it also resulted in a significant reduction in DC migratory capacity toward tumor supernatant and IL8 in vitro. Consistently, LMW HA dramatically enhanced in vivo DC recruitment to tumor-regional lymph nodes and reduced DC migration toward tumor tissue. This study shows that LMW HA--a poorly immunogenic molecule--represents a promising candidate to improve human DC maturation protocols in the context of DC-based vaccines development, due to its ability to enhance their immunogenic properties as well as their migratory capacity toward lymph nodes instead of tumors.", "link"=>"http://www.mendeley.com/research/low-molecular-weight-hyaluronanpulsed-human-dendritic-cells-showed-increased-migration-capacity-indu", "reader_count"=>13, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>2, "Neuroscience"=>2, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Canada"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1682773"], "description"=>"<p>Nude mice received intraperitoneal injections of human-derived CFSE-labeled PBLs (5×10<sup>6</sup>) and allogeneic mature DC/TL, or DC/TL/LMW HA (1,5×10<sup>6</sup>). Proliferation was monitored 48 h later by FACS-gated lymphocytes from peritoneal lavages by quantifying fluorescent dye signal which is inversely correlated to their proliferation rate. Fluorescence intensity in the input undivided lymphocytes was over 95% (gray line in the histogram). a) Three histograms representative of both HD and CRC patients are shown. Gray line: undivided lymphocytes; gray shadow: Lymphocytes + DC/TL; black line: Lymphocytes + DC/TL/LMW HA. b) Bars represent percentage of lymphocyte proliferation increase ± SEM respect to undivided lymphocytes (HD n: 5 and CRC patients n: 5). White bar: lymphocyte alone; gray bar: DC/TL; black bar: DC/TL/LMW HA. *DC/TL vs DC/TL/LMW HA; Paired t test; p≤0.05.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175290, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LMW_HA_treatment_of_DC_enhances_human_T_cell_proliferation_in_vivo_/1175290", "title"=>"LMW HA treatment of DC enhances human T-cell proliferation <i>in vivo.</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-19 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1682776"], "description"=>"<p>a) Migratory ability of DC treated or not with LMW HA toward CCR7 ligand CCL21 (200 ng/ml) was evaluated in a Boyden chamber system. DC were loaded into the upper well of the chamber and CCL21 was added to the lower chamber. Data are expressed as DC/TL and DC/TL/LMW HA migration index. Poly (I:C) was used as a positive control of maturation stimulus. b) CCR7 expression was examined by qPCR. Black bars represent CCR7 fold-change expression in comparison with DC/TL. c) Similar chemotaxis assays were set up placing lymph node supernatant from tumor bearing nude mice in the lower chamber as chemoattractant. Bars represent DC migration index from both HD and CRC patients. Gray bar: DC/TL; black bar: DC/TL/LMW HA; white bar: DC/TL/Poly (I:C). DC/TL vs DC/TL/LMW HA. Mann Whitney t test; * p≤0.05; **p≤0.01.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175293, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LMW_HA_treatment_increases_migratory_response_of_DC_toward_CCL21_inducing_their_CCR7_expression_and_increases_their_migratory_response_toward_lymph_node_supernatant_/1175293", "title"=>"LMW HA treatment increases migratory response of DC toward CCL21 inducing their CCR7 expression and increases their migratory response toward lymph node supernatant.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-19 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1682779"], "description"=>"<p>a) IL-8 expression was evaluated by qPCR. b) Human chemokine antibody array (38 proteins) was performed from tumor culture supernatant. The signal intensity for each antigen-specific antibody spot is proportional to the relative concentration of the antigen in the sample. Gray bars: DC/LT; black bars: DC/TL/LMW HA. Mann Whitney t test; *p≤0,05. * vs. DC/TL.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175296, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_8_expression_is_upregulated_in_LMW_HA_treated_DC_and_is_present_in_tumor_supernatant_/1175296", "title"=>"IL-8 expression is upregulated in LMW HA treated DC and is present in tumor supernatant.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-19 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1682782"], "description"=>"<p>a) Chemotaxis assays were set up placing IL-8 in the lower chamber and LMW HA treated or untreated DC were placed in the upper chamber. b) A similar migration assay was set up placing TCM with addition of a specific antibody against IL-8 (mAbIL-8) or isotype antibody (20 µg/ml) in the bottom chamber as chemoattractant. Graphs represent data from 4 independent experiments similarly performed expressed as migration index respect to DC/TL migration toward TCM; five fields were counted for each quadruplicate well. Gray bars: DC/LT; black bars: DC/TL/LMW HA; white bars: DC/TL/Poly (I:C). Mann Whitney t test; *p≤0,05; ***p≤0,001. * vs. DC/TL.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175298, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LMW_HA_induces_resistance_in_human_DC_to_IL_8_chemoattraction_/1175298", "title"=>"LMW HA induces resistance in human DC to IL-8 chemoattraction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-19 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1682786"], "description"=>"<p>a) MMP activity was analyzed by zymography and quantified by densitometry. Relative MMP activity was obtained by normalizing values to untreated samples (DC/TL). Bars represent MMP activity from HD. b) qPCR of HA receptors was performed. The results are expressed as fold change related to DC/TL. Gray bar: DC/TL; black bar: DC/TL/LMW HA. DC/TL vs DC/TL/LMW HA. Mann Whitney t test; *p≤0,05; ***p≤0,001.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175303, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DC_pre_treated_with_LMW_HA_induces_MMP_activity_and_downregulates_HA_receptors_expression_/1175303", "title"=>"DC pre-treated with LMW HA induces MMP activity and downregulates HA receptors expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-19 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1682787"], "description"=>"<p>DC/TL were or not LMW HA treated, and after CM DiL labeling were inoculated s.c. in human-tumor bearing nude mice. Twenty four hours later lymph nodes (a) and tumors (b) were surgically removed and a cell suspension was obtained from these tissues. Number of fluorescent DC was counted by flow cytometry. The upper panel (a) shows DC/TL migration toward lymph nodes. The lower panel shows migration toward tumor tissue (b). Bars represent the number of migrated DC per individual HD (1–6) and CRC patients (P 1–4). Gray bar: DC/TL; black bar: DC/TL/LMW HA. * DC/TL vs DC/TL/LMW HA. Paired t test; *p≤0,05.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175304, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pre_incubation_of_DC_with_LMW_HA_increases_their_migration_toward_lymph_node_and_reduces_their_tumor_attraction_in_vivo_/1175304", "title"=>"Pre-incubation of DC with LMW HA increases their migration toward lymph node and reduces their tumor attraction <i>in vivo.</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-19 02:44:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1682789"], "description"=>"<p>PBMC-derived DC from healthy donors (HD) and colorectal carcinoma (CRC) patients were stained with mAbs anti-CD11c, MHC-II, CD86, CD83 and CD40. CD11c<sup>+</sup> cells were gated and the co-expression of several markers was analyzed. Data are expressed as geometric mean fluorescence.</p><p>*vs HD DC/LT,</p>δ<p>vs CRC patients DC/TL;</p><p>p≤0,05.</p><p>Phenotipic analyses of LMW HA pre-treated DC.</p>", "links"=>[], "tags"=>["ccl", "crc", "DC migration", "lymph nodes", "LMW HA treatment", "vivo DC recruitment", "LMW HA", "LWM", "DC maturation protocols", "leucocyte reaction activity", "il", "CCR 7 expression levels"], "article_id"=>1175306, "categories"=>["Uncategorised"], "users"=>["Manglio Rizzo", "Juan Bayo", "Flavia Piccioni", "Mariana Malvicini", "Esteban Fiore", "Estanislao Peixoto", "Mariana G. Garcia", "Jorge B. Aquino", "Ariel Gonzalez Campaña", "Gustavo Podestá", "Marcelo Terres", "Oscar Andriani", "Laura Alaniz", "Guillermo Mazzolini"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107944.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotipic_analyses_of_LMW_HA_pre_treated_DC_/1175306", "title"=>"Phenotipic analyses of LMW HA pre-treated DC.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-19 02:44:32"}

PMC Usage Stats | Further Information

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Relative Metric

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