Interleukin-6 Modulates Graft-versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation
Identifieur interne : 003B87 ( Main/Exploration ); précédent : 003B86; suivant : 003B88Interleukin-6 Modulates Graft-versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation
Auteurs : Isao Tawara [États-Unis] ; Motoko Koyama [Australie] ; CHEN LIU [États-Unis] ; Tomomi Toubai [États-Unis] ; Dafydd Thomas [États-Unis] ; Rebecca Evers [États-Unis] ; Peter Chockley [États-Unis] ; Evelyn Nieves [États-Unis] ; YAPING SUN [États-Unis] ; Kathleen P. Lowler [États-Unis] ; Chelsea Malter [États-Unis] ; Norihiro Nishimoto [Japon] ; Geoffrey R. Hill [Australie] ; Pavan Reddy [États-Unis]Source :
- Clinical cancer research [ 1078-0432 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux, Anticorps monoclonaux (pharmacologie), Femelle, Interleukine-6 (antagonistes et inhibiteurs), Interleukine-6 (déficit), Interleukine-6 (immunologie), Maladie du greffon contre l'hôte (), Maladie du greffon contre l'hôte (immunologie), Souris, Souris de lignée BALB C, Souris de lignée C3H, Souris de lignée C57BL, Souris de lignée DBA, Souris de souche-129, Transplantation de moelle osseuse (immunologie), Transplantation homologue.
- MESH :
- antagonistes et inhibiteurs : Interleukine-6.
- déficit : Interleukine-6.
- immunologie : Interleukine-6, Maladie du greffon contre l'hôte, Transplantation de moelle osseuse.
- pharmacologie : Anticorps monoclonaux.
- Pascal (Inist)
- Animaux, Femelle, Interleukine 6, Cellule souche, Cellule hématopoïétique, Homogreffe, Maladie du greffon contre l'hôte, Moelle osseuse, Allogreffe de moelle osseuse, Souris, Souris de lignée BALB C, Souris de lignée C3H, Souris de lignée C57BL, Souris de lignée DBA, Souris de souche-129, Transplantation homologue.
- Wicri :
- topic : Cellule souche.
English descriptors
- KwdEn :
- Allogeneic bone marrow transplantation, Animals, Antibodies, Monoclonal (pharmacology), Bone Marrow Transplantation (immunology), Bone marrow, Female, Graft vs Host Disease (immunology), Graft vs Host Disease (therapy), Hematopoietic cell, Homograft, Interleukin 6, Interleukin-6 (antagonists & inhibitors), Interleukin-6 (deficiency), Interleukin-6 (immunology), Mice, Mice, 129 Strain, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Stem cell, Transplantation, Homologous.
- MESH :
- chemical , antagonists & inhibitors : Interleukin-6.
- chemical , deficiency : Interleukin-6.
- chemical , immunology : Interleukin-6.
- chemical , pharmacology : Antibodies, Monoclonal.
- immunology : Bone Marrow Transplantation, Graft vs Host Disease.
- therapy : Graft vs Host Disease.
- Animals, Female, Mice, Mice, 129 Strain, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Transplantation, Homologous.
Abstract
Purpose: The graft-versus-tumor (GVT) effect is a potent form of immunotherapy against many hematologic malignancies and some solid tumors. The beneficial GVT effect after allogeneic bone marrow transplantation (BMT) is tightly linked to its most significant complication, graft-versus-host disease (GVHD). The role of interleukin-6 (IL-6) after allogeneic BMT is not well understood. This study used a series of complementary knockout and antibody blockade strategies to analyze the impact of IL-6 in multiple clinically relevant murine models of GVHD and GVT. Experimental Design: We examined the effect of the source of IL-6 by analyzing the role IL-6 deficiency in donor T cells, donor bone marrow or in host tissues. We confirmed and extended the relevance of IL-6 deficiency on GVHD and GVT by treating BMT recipients with anti-mouse IL-6 receptor (IL-6R), MR16-1. Results: Deficiency of IL-6 in donor T cells led to prolongation of survival. Total inhibition of IL-6 with MR16-1 caused an even greater reduction in GVHD-induced mortality. The reduction in GVHD was independent of the direct effects on T effector cell expansion or donor regulatory T cells. GVT responses were preserved after treatment with MR16-1. Conclusion: MR16-1 treatment reduced GVHD and preserved sufficient GVT. Tocilizumab, a humanized anti-IL-6R monoclonal antibody (mAb), is approved in several countries including the United States and European Union for the treatment of rheumatoid arthritis and other inflammatory diseases. Blockade of IL-6 with anti-IL-6R mAb therapy may be testable in clinical trials as an adjunct to prevent GVHD in BMT patients without a significant loss of GVT.
Affiliations:
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last="Yaping Sun">YAPING SUN</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Lowler, Kathleen P" sort="Lowler, Kathleen P" uniqKey="Lowler K" first="Kathleen P." last="Lowler">Kathleen P. 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Hill</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Immunology, Bone Marrow Transplant Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Reddy, Pavan" sort="Reddy, Pavan" uniqKey="Reddy P" first="Pavan" last="Reddy">Pavan Reddy</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno 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aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Koyama, Motoko" sort="Koyama, Motoko" uniqKey="Koyama M" first="Motoko" last="Koyama">Motoko Koyama</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Immunology, Bone Marrow Transplant Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Chen Liu" sort="Chen Liu" uniqKey="Chen Liu" last="Chen Liu">CHEN LIU</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Pathology, University of Florida College of Medicine</s1><s2>Gainesville, Florida</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Toubai, Tomomi" sort="Toubai, Tomomi" uniqKey="Toubai T" first="Tomomi" last="Toubai">Tomomi Toubai</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Thomas, Dafydd" sort="Thomas, Dafydd" uniqKey="Thomas D" first="Dafydd" last="Thomas">Dafydd Thomas</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Pathology, University of Michigan</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Evers, Rebecca" sort="Evers, Rebecca" uniqKey="Evers R" first="Rebecca" last="Evers">Rebecca Evers</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Chockley, Peter" sort="Chockley, Peter" uniqKey="Chockley P" first="Peter" last="Chockley">Peter Chockley</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Nieves, Evelyn" sort="Nieves, Evelyn" uniqKey="Nieves E" first="Evelyn" last="Nieves">Evelyn Nieves</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Yaping Sun" sort="Yaping Sun" uniqKey="Yaping Sun" last="Yaping Sun">YAPING SUN</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Lowler, Kathleen P" sort="Lowler, Kathleen P" uniqKey="Lowler K" first="Kathleen P." last="Lowler">Kathleen P. Lowler</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Malter, Chelsea" sort="Malter, Chelsea" uniqKey="Malter C" first="Chelsea" last="Malter">Chelsea Malter</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Nishimoto, Norihiro" sort="Nishimoto, Norihiro" uniqKey="Nishimoto N" first="Norihiro" last="Nishimoto">Norihiro Nishimoto</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Laboratory of Immune Regulation, Wakayama Medical University</s1><s2>Ibaraki-City, Osaka</s2><s3>JPN</s3><sZ>12 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Ibaraki-City, Osaka</wicri:noRegion></affiliation></author><author><name sortKey="Hill, Geoffrey R" sort="Hill, Geoffrey R" uniqKey="Hill G" first="Geoffrey R." last="Hill">Geoffrey R. Hill</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Immunology, Bone Marrow Transplant Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Reddy, Pavan" sort="Reddy, Pavan" uniqKey="Reddy P" first="Pavan" last="Reddy">Pavan Reddy</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Internal Medicine and University of Michigan Comprehensive Cancer Center</s1><s2>Ann Arbor, Michigan</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Clinical cancer research</title><title level="j" type="abbreviated">Clin. cancer res.</title><idno type="ISSN">1078-0432</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Clinical cancer research</title><title level="j" type="abbreviated">Clin. cancer res.</title><idno type="ISSN">1078-0432</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allogeneic bone marrow transplantation</term><term>Animals</term><term>Antibodies, Monoclonal (pharmacology)</term><term>Bone Marrow Transplantation (immunology)</term><term>Bone marrow</term><term>Female</term><term>Graft vs Host Disease (immunology)</term><term>Graft vs Host Disease (therapy)</term><term>Hematopoietic cell</term><term>Homograft</term><term>Interleukin 6</term><term>Interleukin-6 (antagonists & inhibitors)</term><term>Interleukin-6 (deficiency)</term><term>Interleukin-6 (immunology)</term><term>Mice</term><term>Mice, 129 Strain</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C3H</term><term>Mice, Inbred C57BL</term><term>Mice, Inbred DBA</term><term>Stem cell</term><term>Transplantation, Homologous</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps monoclonaux (pharmacologie)</term><term>Femelle</term><term>Interleukine-6 (antagonistes et inhibiteurs)</term><term>Interleukine-6 (déficit)</term><term>Interleukine-6 (immunologie)</term><term>Maladie du greffon contre l'hôte ()</term><term>Maladie du greffon contre l'hôte (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée C3H</term><term>Souris de lignée C57BL</term><term>Souris de lignée DBA</term><term>Souris de souche-129</term><term>Transplantation de moelle osseuse (immunologie)</term><term>Transplantation homologue</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Interleukine-6</term><term>Maladie du greffon contre l'hôte</term><term>Transplantation de moelle osseuse</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Bone Marrow Transplantation</term><term>Graft vs Host Disease</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Anticorps monoclonaux</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Graft vs Host Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Mice</term><term>Mice, 129 Strain</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C3H</term><term>Mice, Inbred C57BL</term><term>Mice, Inbred DBA</term><term>Transplantation, Homologous</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Interleukine 6</term><term>Cellule souche</term><term>Cellule hématopoïétique</term><term>Homogreffe</term><term>Maladie du greffon contre l'hôte</term><term>Moelle osseuse</term><term>Allogreffe de moelle osseuse</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée C3H</term><term>Souris de lignée C57BL</term><term>Souris de lignée DBA</term><term>Souris de souche-129</term><term>Transplantation homologue</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Cellule souche</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Purpose: The graft-versus-tumor (GVT) effect is a potent form of immunotherapy against many hematologic malignancies and some solid tumors. The beneficial GVT effect after allogeneic bone marrow transplantation (BMT) is tightly linked to its most significant complication, graft-versus-host disease (GVHD). The role of interleukin-6 (IL-6) after allogeneic BMT is not well understood. This study used a series of complementary knockout and antibody blockade strategies to analyze the impact of IL-6 in multiple clinically relevant murine models of GVHD and GVT. Experimental Design: We examined the effect of the source of IL-6 by analyzing the role IL-6 deficiency in donor T cells, donor bone marrow or in host tissues. We confirmed and extended the relevance of IL-6 deficiency on GVHD and GVT by treating BMT recipients with anti-mouse IL-6 receptor (IL-6R), MR16-1. Results: Deficiency of IL-6 in donor T cells led to prolongation of survival. Total inhibition of IL-6 with MR16-1 caused an even greater reduction in GVHD-induced mortality. The reduction in GVHD was independent of the direct effects on T effector cell expansion or donor regulatory T cells. GVT responses were preserved after treatment with MR16-1. Conclusion: MR16-1 treatment reduced GVHD and preserved sufficient GVT. Tocilizumab, a humanized anti-IL-6R monoclonal antibody (mAb), is approved in several countries including the United States and European Union for the treatment of rheumatoid arthritis and other inflammatory diseases. Blockade of IL-6 with anti-IL-6R mAb therapy may be testable in clinical trials as an adjunct to prevent GVHD in BMT patients without a significant loss of GVT.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Japon</li><li>États-Unis</li></country><region><li>Floride</li><li>Michigan</li></region></list><tree><country name="États-Unis"><region name="Michigan"><name sortKey="Tawara, Isao" sort="Tawara, Isao" uniqKey="Tawara I" first="Isao" last="Tawara">Isao Tawara</name></region><name sortKey="Chen Liu" sort="Chen Liu" uniqKey="Chen Liu" last="Chen Liu">CHEN LIU</name><name sortKey="Chockley, Peter" sort="Chockley, Peter" uniqKey="Chockley P" first="Peter" last="Chockley">Peter Chockley</name><name sortKey="Evers, Rebecca" sort="Evers, Rebecca" uniqKey="Evers R" first="Rebecca" last="Evers">Rebecca Evers</name><name sortKey="Lowler, Kathleen P" sort="Lowler, Kathleen P" uniqKey="Lowler K" first="Kathleen P." last="Lowler">Kathleen P. Lowler</name><name sortKey="Malter, Chelsea" sort="Malter, Chelsea" uniqKey="Malter C" first="Chelsea" last="Malter">Chelsea Malter</name><name sortKey="Nieves, Evelyn" sort="Nieves, Evelyn" uniqKey="Nieves E" first="Evelyn" last="Nieves">Evelyn Nieves</name><name sortKey="Reddy, Pavan" sort="Reddy, Pavan" uniqKey="Reddy P" first="Pavan" last="Reddy">Pavan Reddy</name><name sortKey="Thomas, Dafydd" sort="Thomas, Dafydd" uniqKey="Thomas D" first="Dafydd" last="Thomas">Dafydd Thomas</name><name sortKey="Thomas, Dafydd" sort="Thomas, Dafydd" uniqKey="Thomas D" first="Dafydd" last="Thomas">Dafydd Thomas</name><name sortKey="Toubai, Tomomi" sort="Toubai, Tomomi" uniqKey="Toubai T" first="Tomomi" last="Toubai">Tomomi Toubai</name><name sortKey="Yaping Sun" sort="Yaping Sun" uniqKey="Yaping Sun" last="Yaping Sun">YAPING SUN</name></country><country name="Australie"><noRegion><name sortKey="Koyama, Motoko" sort="Koyama, Motoko" uniqKey="Koyama M" first="Motoko" last="Koyama">Motoko Koyama</name></noRegion><name sortKey="Hill, Geoffrey R" sort="Hill, Geoffrey R" uniqKey="Hill G" first="Geoffrey R." last="Hill">Geoffrey R. Hill</name></country><country name="Japon"><noRegion><name sortKey="Nishimoto, Norihiro" sort="Nishimoto, Norihiro" uniqKey="Nishimoto N" first="Norihiro" last="Nishimoto">Norihiro Nishimoto</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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