Alloimmune Activation Promotes Anti-Cancer Cytotoxicity after Rat Liver Transplantation
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{"title"=>"Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation", "type"=>"journal", "authors"=>[{"first_name"=>"Stéphanie", "last_name"=>"Lacotte", "scopus_author_id"=>"14060646800"}, {"first_name"=>"Graziano", "last_name"=>"Oldani", "scopus_author_id"=>"12761433100"}, {"first_name"=>"Florence", "last_name"=>"Slits", "scopus_author_id"=>"56162776400"}, {"first_name"=>"Lorenzo A.", "last_name"=>"Orci", "scopus_author_id"=>"55504415900"}, {"first_name"=>"Laura", "last_name"=>"Rubbia-Brandt", "scopus_author_id"=>"7003369677"}, {"first_name"=>"Philippe", "last_name"=>"Morel", "scopus_author_id"=>"36038296900"}, {"first_name"=>"Gilles", "last_name"=>"Mentha", "scopus_author_id"=>"35227708200"}, {"first_name"=>"Christian", "last_name"=>"Toso", "scopus_author_id"=>"7003329536"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"24651497", "pui"=>"372852126", "scopus"=>"2-s2.0-84925283277", "doi"=>"10.1371/journal.pone.0091515", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84925283277"}, "id"=>"5a93efea-5afa-3210-846f-28f85a3adc0b", "abstract"=>"Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.", "link"=>"http://www.mendeley.com/research/alloimmune-activation-promotes-anticancer-cytotoxicity-after-rat-liver-transplantation", "reader_count"=>3, "reader_count_by_academic_status"=>{"Other"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Other"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1429478/Figure_1.tif"], "description"=>"<p>(A) Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels after allogeneic Dark Agouti-to-Lewis (black) and syngeneic Lewis-to-Lewis (white) rat liver transplantations. (B) Bilirubine levels after allogeneic (black) and syngeneic (white) transplantation. (C) Representative hematoxilin-eosin stained biopsies on day 10 after allogeneic (right) and syngeneic (left) rat liver transplantation. (D) Post-transplant blood CD4/CD8 ratios on day 7 (D7) and 11 (D11). (E) IFNγ secretion after peripheral blood mononuclear cells (PBMC) mixed lymphocyte reaction on day ten post-transplantation with donor (DA) and third part stimulation. *p<0.05, **<0.01.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Molecular cell biology", "immunology", "Immune response", "Gastroenterology and hepatology", "oncology", "Basic cancer research", "Surgical and invasive medical procedures", "transplantation", "alloimmunity"], "article_id"=>969383, "categories"=>["Biological Sciences"], "users"=>["Stéphanie Lacotte", "Graziano Oldani", "Florence Slits", "Lorenzo A. Orci", "Laura Rubbia-Brandt", "Philippe Morel", "Gilles Mentha", "Christian Toso"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0091515.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Assessment_of_alloimmunity_and_rejection_/969383", "title"=>"Assessment of alloimmunity and rejection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-20 04:34:54"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1429479/Figure_2.tif"], "description"=>"<p>(A) <i>Ex vivo</i> PBMC anti-cancer cytotoxicity on day ten after allogeneic and syngeneic transplantations and in naïve control rats at various effector/target ratio (E/T). (B) Frequency of NKRP1<sup>high</sup> cells (NK cells) among PBMCs on day 7 (D7) and 10 (D10) after transplantation. Flow cytometry dot-plot assessed the gating strategy. (C) Flow cytometry dot-plot and histogram assessing the gating strategy for monocytes/macrophages (CD172+) and NKRP1 expression level on CD172+ cells. (D) Frequency of monocyte/macrophage (CD172+ cells) among PBMCs. (E) Activation level of monocyte/macrophages (NKRP1 expression level (mean fluorescence intensity (MFI)) among CD172a+ cells). *p<0.05, **<0.01.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Molecular cell biology", "immunology", "Immune response", "Gastroenterology and hepatology", "oncology", "Basic cancer research", "Surgical and invasive medical procedures", "transplantation", "peripheral"], "article_id"=>969384, "categories"=>["Biological Sciences"], "users"=>["Stéphanie Lacotte", "Graziano Oldani", "Florence Slits", "Lorenzo A. Orci", "Laura Rubbia-Brandt", "Philippe Morel", "Gilles Mentha", "Christian Toso"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0091515.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Alloimmunity_associated_peripheral_cytotoxicity_/969384", "title"=>"Alloimmunity-associated peripheral cytotoxicity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-20 04:34:54"}
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  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1429483/Figure_5.tif"], "description"=>"<p>(A) Liver expression of <i>nkg2d</i> on day ten after liver transplantation. (B) Representative NKG2D expression levels in blood NK cells (left) and monocytes (right) of allogeneic (black) and syngeneic (grey) recipients. Isotype was used as control (dashed lines). (C) Sorted blood NK cell cytotoxicity inhibition with anti-NKG2D antibody or with anti-NKp30 antibody. (D) Levels of NKG2D ligand (<i>rae1l, rrlt</i> and <i>irp94</i>) expression in the liver on day ten after transplantation. (E) Levels of NKG2D ligand (<i>rae1l</i>, <i>rrlt</i> and <i>irp94</i>) expression in rat HCC cell lines. (F) Representative level of recombinant NKG2D-Fc binding to rat HCC cells lines. *p<0.05, **<0.01.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "Immune cells", "Molecular cell biology", "immunology", "Immune response", "Gastroenterology and hepatology", "oncology", "Basic cancer research", "Surgical and invasive medical procedures", "transplantation", "cytotoxicity", "mediated", "nkg2d"], "article_id"=>969388, "categories"=>["Biological Sciences"], "users"=>["Stéphanie Lacotte", "Graziano Oldani", "Florence Slits", "Lorenzo A. Orci", "Laura Rubbia-Brandt", "Philippe Morel", "Gilles Mentha", "Christian Toso"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0091515.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Alloimmunity_associated_cytotoxicity_is_mediated_through_the_NKG2D_receptor_/969388", "title"=>"Alloimmunity-associated cytotoxicity is mediated through the NKG2D receptor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-20 04:34:54"}

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