Autophagy inhibition upregulates CD4+ tumor infiltrating lymphocyte expression via miR-155 regulation and TRAIL activation.
Identifieur interne : 000D76 ( Main/Exploration ); précédent : 000D75; suivant : 000D77Autophagy inhibition upregulates CD4+ tumor infiltrating lymphocyte expression via miR-155 regulation and TRAIL activation.
Auteurs : Paul Zarogoulidis [Grèce] ; Savvas Petanidis [Grèce] ; Kalliopi Domvri [Grèce] ; Efrosini Kioseoglou [Grèce] ; Doxakis Anestakis [Grèce] ; Lutz Freitag [Allemagne] ; Konstantinos Zarogoulidis [Grèce] ; Wolfgang Hohenforst-Schmidt [Allemagne] ; Wilfried Eberhardt [Allemagne]Source :
- Molecular oncology [ 1878-0261 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Antinéoplasiques (pharmacologie), Antinéoplasiques (usage thérapeutique), Antirhumatismaux (pharmacologie), Antirhumatismaux (usage thérapeutique), Apoptose (), Autophagie (), Carboplatine (pharmacologie), Carboplatine (usage thérapeutique), Carcinome pulmonaire non à petites cellules (anatomopathologie), Carcinome pulmonaire non à petites cellules (immunologie), Carcinome pulmonaire non à petites cellules (secondaire), Carcinome pulmonaire non à petites cellules (traitement médicamenteux), Chloroquine (pharmacologie), Chloroquine (usage thérapeutique), Humains, Ligand TRAIL (immunologie), Lymphocytes T CD4+ (), Lymphocytes T CD4+ (anatomopathologie), Lymphocytes T CD4+ (immunologie), Lymphocytes TIL (), Lymphocytes TIL (anatomopathologie), Lymphocytes TIL (immunologie), Poumon (), Poumon (anatomopathologie), Poumon (immunologie), Régulation de l'expression des gènes tumoraux (), Résistance aux médicaments antinéoplasiques (), Sujet âgé, Sujet âgé de 80 ans ou plus, Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (immunologie), Tumeurs du poumon (secondaire), Tumeurs du poumon (traitement médicamenteux), microARN (génétique), microARN (immunologie).
- MESH :
- anatomopathologie : Carcinome pulmonaire non à petites cellules, Lymphocytes T CD4+, Lymphocytes TIL, Poumon, Tumeurs du poumon.
- génétique : microARN.
- immunologie : Carcinome pulmonaire non à petites cellules, Ligand TRAIL, Lymphocytes T CD4+, Lymphocytes TIL, Poumon, Tumeurs du poumon, microARN.
- pharmacologie : Antinéoplasiques, Antirhumatismaux, Carboplatine, Chloroquine.
- secondaire : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- traitement médicamenteux : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- usage thérapeutique : Antinéoplasiques, Antirhumatismaux, Carboplatine, Chloroquine.
- Adulte, Adulte d'âge moyen, Apoptose, Autophagie, Humains, Lymphocytes T CD4+, Lymphocytes TIL, Poumon, Régulation de l'expression des gènes tumoraux, Résistance aux médicaments antinéoplasiques, Sujet âgé, Sujet âgé de 80 ans ou plus.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents (pharmacology), Antineoplastic Agents (therapeutic use), Antirheumatic Agents (pharmacology), Antirheumatic Agents (therapeutic use), Apoptosis (drug effects), Autophagy (drug effects), CD4-Positive T-Lymphocytes (drug effects), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (pathology), Carboplatin (pharmacology), Carboplatin (therapeutic use), Carcinoma, Non-Small-Cell Lung (drug therapy), Carcinoma, Non-Small-Cell Lung (immunology), Carcinoma, Non-Small-Cell Lung (pathology), Carcinoma, Non-Small-Cell Lung (secondary), Chloroquine (pharmacology), Chloroquine (therapeutic use), Drug Resistance, Neoplasm (drug effects), Gene Expression Regulation, Neoplastic (drug effects), Humans, Lung (drug effects), Lung (immunology), Lung (pathology), Lung Neoplasms (drug therapy), Lung Neoplasms (immunology), Lung Neoplasms (pathology), Lung Neoplasms (secondary), Lymphocytes, Tumor-Infiltrating (drug effects), Lymphocytes, Tumor-Infiltrating (immunology), Lymphocytes, Tumor-Infiltrating (pathology), MicroRNAs (genetics), MicroRNAs (immunology), Middle Aged, TNF-Related Apoptosis-Inducing Ligand (immunology).
- MESH :
- chemical , genetics : MicroRNAs.
- chemical , immunology : MicroRNAs, TNF-Related Apoptosis-Inducing Ligand.
- chemical , pharmacology : Antineoplastic Agents, Antirheumatic Agents, Carboplatin, Chloroquine.
- chemical , therapeutic use : Antineoplastic Agents, Antirheumatic Agents, Carboplatin, Chloroquine.
- drug effects : Apoptosis, Autophagy, CD4-Positive T-Lymphocytes, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Lung, Lymphocytes, Tumor-Infiltrating.
- drug therapy : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- immunology : CD4-Positive T-Lymphocytes, Carcinoma, Non-Small-Cell Lung, Lung, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating.
- pathology : CD4-Positive T-Lymphocytes, Carcinoma, Non-Small-Cell Lung, Lung, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating.
- secondary : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- Adult, Aged, Aged, 80 and over, Humans, Middle Aged.
Abstract
Chemoresistance is a major challenge in lung cancer treatment. Recent findings have revealed that autophagic mechanism contributes significantly to immunosuppressive related chemoresistance. For that reason, targeting autophagy-related immunosuppression is an important approach to reverse tumor drug resistance. In this study, we report for the first time that autophagy inhibition triggers upregulation of CD4+, Foxp3+ tumor infiltrating lymphocytes in late metastatic lung cancer tissues. Furthermore, autophagy blockage induces chemosensitization to carboplatin, immune activation and cell cycle arrest. This induction correlated with reduction in expression of drug resistance genes MDR1, MRP1, ABCG2 and ABCC2 along with decreased expression of PD-L1 which is associated with severe dysfunction of tumor specific CD8+ T cells. Furthermore, experiments revealed that co-treatment of carboplatin and autophagy inhibitor chloroquine increased lung tissue infiltration by CD4+, FoxP3+ lymphocytes and antigen-specific immune activation. Subsequent ex vivo experiments showed the activation of carboplatin related TRAIL-dependent apoptosis through caspase 8 and a synergistic role of miR-155 in lung tissue infiltration by CD4+, and FoxP3+ lymphocytes. Overall, our results indicate that autophagy blockage increases lung cancer chemosensitivity to carboplatin, but also reveal that miR-155 functions as a novel immune system activator by promoting TILs infiltration. These results indicate that targeting of autophagy can prevent cancer related immunosuppression and elucidate immune cell infiltration in tumor microenvironment thus representing a potential therapeutic strategy to inhibit lung cancer progression and metastasis.
DOI: 10.1016/j.molonc.2016.08.005
PubMed: 27692344
Affiliations:
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Le document en format XML
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Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010</wicri:regionArea><wicri:noRegion>57010</wicri:noRegion></affiliation></author><author><name sortKey="Petanidis, Savvas" sort="Petanidis, Savvas" uniqKey="Petanidis S" first="Savvas" last="Petanidis">Savvas Petanidis</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece. Electronic address: spetanid@auth.gr.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124</wicri:regionArea><wicri:noRegion>54124</wicri:noRegion></affiliation></author><author><name sortKey="Domvri, Kalliopi" sort="Domvri, Kalliopi" uniqKey="Domvri K" first="Kalliopi" last="Domvri">Kalliopi Domvri</name><affiliation wicri:level="1"><nlm:affiliation>Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010</wicri:regionArea><wicri:noRegion>57010</wicri:noRegion></affiliation></author><author><name sortKey="Kioseoglou, Efrosini" sort="Kioseoglou, Efrosini" uniqKey="Kioseoglou E" first="Efrosini" last="Kioseoglou">Efrosini Kioseoglou</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, 54124</wicri:regionArea><wicri:noRegion>54124</wicri:noRegion></affiliation></author><author><name sortKey="Anestakis, Doxakis" sort="Anestakis, Doxakis" uniqKey="Anestakis D" first="Doxakis" last="Anestakis">Doxakis Anestakis</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Laboratory of General Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece; Department of Medicine, Laboratory of Forensic Medicine and Toxicology, Aristotle University of Thessaloniki, 54124, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Medicine, Laboratory of General Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece; Department of Medicine, Laboratory of Forensic Medicine and Toxicology, Aristotle University of Thessaloniki, 54124</wicri:regionArea><wicri:noRegion>54124</wicri:noRegion></affiliation></author><author><name sortKey="Freitag, Lutz" sort="Freitag, Lutz" uniqKey="Freitag L" first="Lutz" last="Freitag">Lutz Freitag</name><affiliation wicri:level="1"><nlm:affiliation>Department of Interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Essen-Duisburg, Tueschener Weg 40, 45239, Essen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Essen-Duisburg, Tueschener Weg 40, 45239, Essen</wicri:regionArea><wicri:noRegion>45239, Essen</wicri:noRegion><wicri:noRegion>45239, Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author><author><name sortKey="Zarogoulidis, Konstantinos" sort="Zarogoulidis, Konstantinos" uniqKey="Zarogoulidis K" first="Konstantinos" last="Zarogoulidis">Konstantinos Zarogoulidis</name><affiliation wicri:level="1"><nlm:affiliation>Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010, Greece.</nlm:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010</wicri:regionArea><wicri:noRegion>57010</wicri:noRegion></affiliation></author><author><name sortKey="Hohenforst Schmidt, Wolfgang" sort="Hohenforst Schmidt, Wolfgang" uniqKey="Hohenforst Schmidt W" first="Wolfgang" last="Hohenforst-Schmidt">Wolfgang Hohenforst-Schmidt</name><affiliation wicri:level="1"><nlm:affiliation>Medical Clinic I, "Fuerth" Hospital, University of Erlangen, 91054, Fuerth, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Medical Clinic I, "Fuerth" Hospital, University of Erlangen, 91054, Fuerth</wicri:regionArea><wicri:noRegion>91054, Fuerth</wicri:noRegion><wicri:noRegion>91054, Fuerth</wicri:noRegion><wicri:noRegion>Fuerth</wicri:noRegion></affiliation></author><author><name sortKey="Eberhardt, Wilfried" sort="Eberhardt, Wilfried" uniqKey="Eberhardt W" first="Wilfried" last="Eberhardt">Wilfried Eberhardt</name><affiliation wicri:level="1"><nlm:affiliation>Division of Thoracic Oncology, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Thoracic Oncology, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122, Essen</wicri:regionArea><wicri:noRegion>45122, Essen</wicri:noRegion><wicri:noRegion>45122, Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular oncology</title><idno type="eISSN">1878-0261</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Antineoplastic Agents (pharmacology)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Antirheumatic Agents (pharmacology)</term><term>Antirheumatic Agents (therapeutic use)</term><term>Apoptosis (drug effects)</term><term>Autophagy (drug effects)</term><term>CD4-Positive T-Lymphocytes (drug effects)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>CD4-Positive T-Lymphocytes (pathology)</term><term>Carboplatin (pharmacology)</term><term>Carboplatin (therapeutic use)</term><term>Carcinoma, Non-Small-Cell Lung (drug therapy)</term><term>Carcinoma, Non-Small-Cell Lung (immunology)</term><term>Carcinoma, Non-Small-Cell Lung (pathology)</term><term>Carcinoma, Non-Small-Cell Lung (secondary)</term><term>Chloroquine (pharmacology)</term><term>Chloroquine (therapeutic use)</term><term>Drug Resistance, Neoplasm (drug effects)</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>Humans</term><term>Lung (drug effects)</term><term>Lung (immunology)</term><term>Lung (pathology)</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (immunology)</term><term>Lung Neoplasms (pathology)</term><term>Lung Neoplasms (secondary)</term><term>Lymphocytes, Tumor-Infiltrating (drug effects)</term><term>Lymphocytes, Tumor-Infiltrating (immunology)</term><term>Lymphocytes, Tumor-Infiltrating (pathology)</term><term>MicroRNAs (genetics)</term><term>MicroRNAs (immunology)</term><term>Middle Aged</term><term>TNF-Related Apoptosis-Inducing Ligand (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Antinéoplasiques (pharmacologie)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Antirhumatismaux (pharmacologie)</term><term>Antirhumatismaux (usage thérapeutique)</term><term>Apoptose ()</term><term>Autophagie ()</term><term>Carboplatine (pharmacologie)</term><term>Carboplatine (usage thérapeutique)</term><term>Carcinome pulmonaire non à petites cellules (anatomopathologie)</term><term>Carcinome pulmonaire non à petites cellules (immunologie)</term><term>Carcinome pulmonaire non à petites cellules (secondaire)</term><term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term><term>Chloroquine (pharmacologie)</term><term>Chloroquine (usage thérapeutique)</term><term>Humains</term><term>Ligand TRAIL (immunologie)</term><term>Lymphocytes T CD4+ ()</term><term>Lymphocytes T CD4+ (anatomopathologie)</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes TIL ()</term><term>Lymphocytes TIL (anatomopathologie)</term><term>Lymphocytes TIL (immunologie)</term><term>Poumon ()</term><term>Poumon (anatomopathologie)</term><term>Poumon (immunologie)</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Résistance aux médicaments antinéoplasiques ()</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (immunologie)</term><term>Tumeurs du poumon (secondaire)</term><term>Tumeurs du poumon (traitement médicamenteux)</term><term>microARN (génétique)</term><term>microARN (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>MicroRNAs</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>MicroRNAs</term><term>TNF-Related Apoptosis-Inducing Ligand</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Antirheumatic Agents</term><term>Carboplatin</term><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term><term>Antirheumatic Agents</term><term>Carboplatin</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Lymphocytes T CD4+</term><term>Lymphocytes TIL</term><term>Poumon</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term><term>CD4-Positive T-Lymphocytes</term><term>Drug Resistance, Neoplasm</term><term>Gene Expression Regulation, Neoplastic</term><term>Lung</term><term>Lymphocytes, Tumor-Infiltrating</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>microARN</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Ligand TRAIL</term><term>Lymphocytes T CD4+</term><term>Lymphocytes TIL</term><term>Poumon</term><term>Tumeurs du poumon</term><term>microARN</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung</term><term>Lung Neoplasms</term><term>Lymphocytes, Tumor-Infiltrating</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung</term><term>Lung Neoplasms</term><term>Lymphocytes, Tumor-Infiltrating</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Antirhumatismaux</term><term>Carboplatine</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques</term><term>Antirhumatismaux</term><term>Carboplatine</term><term>Chloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Humans</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Apoptose</term><term>Autophagie</term><term>Humains</term><term>Lymphocytes T CD4+</term><term>Lymphocytes TIL</term><term>Poumon</term><term>Régulation de l'expression des gènes tumoraux</term><term>Résistance aux médicaments antinéoplasiques</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Chemoresistance is a major challenge in lung cancer treatment. Recent findings have revealed that autophagic mechanism contributes significantly to immunosuppressive related chemoresistance. For that reason, targeting autophagy-related immunosuppression is an important approach to reverse tumor drug resistance. In this study, we report for the first time that autophagy inhibition triggers upregulation of CD4<sup>+</sup>, Foxp3<sup>+</sup> tumor infiltrating lymphocytes in late metastatic lung cancer tissues. Furthermore, autophagy blockage induces chemosensitization to carboplatin, immune activation and cell cycle arrest. This induction correlated with reduction in expression of drug resistance genes MDR1, MRP1, ABCG2 and ABCC2 along with decreased expression of PD-L1 which is associated with severe dysfunction of tumor specific CD8<sup>+</sup> T cells. Furthermore, experiments revealed that co-treatment of carboplatin and autophagy inhibitor chloroquine increased lung tissue infiltration by CD4<sup>+</sup>, FoxP3<sup>+</sup> lymphocytes and antigen-specific immune activation. Subsequent ex vivo experiments showed the activation of carboplatin related TRAIL-dependent apoptosis through caspase 8 and a synergistic role of miR-155 in lung tissue infiltration by CD4<sup>+</sup>, and FoxP3<sup>+</sup> lymphocytes. Overall, our results indicate that autophagy blockage increases lung cancer chemosensitivity to carboplatin, but also reveal that miR-155 functions as a novel immune system activator by promoting TILs infiltration. These results indicate that targeting of autophagy can prevent cancer related immunosuppression and elucidate immune cell infiltration in tumor microenvironment thus representing a potential therapeutic strategy to inhibit lung cancer progression and metastasis.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Grèce</li></country></list><tree><country name="Grèce"><noRegion><name sortKey="Zarogoulidis, Paul" sort="Zarogoulidis, Paul" uniqKey="Zarogoulidis P" first="Paul" last="Zarogoulidis">Paul Zarogoulidis</name></noRegion><name sortKey="Anestakis, Doxakis" sort="Anestakis, Doxakis" uniqKey="Anestakis D" first="Doxakis" last="Anestakis">Doxakis Anestakis</name><name sortKey="Domvri, Kalliopi" sort="Domvri, Kalliopi" uniqKey="Domvri K" first="Kalliopi" last="Domvri">Kalliopi Domvri</name><name sortKey="Kioseoglou, Efrosini" sort="Kioseoglou, Efrosini" uniqKey="Kioseoglou E" first="Efrosini" last="Kioseoglou">Efrosini Kioseoglou</name><name sortKey="Petanidis, Savvas" sort="Petanidis, Savvas" uniqKey="Petanidis S" first="Savvas" last="Petanidis">Savvas Petanidis</name><name sortKey="Zarogoulidis, Konstantinos" sort="Zarogoulidis, Konstantinos" uniqKey="Zarogoulidis K" first="Konstantinos" last="Zarogoulidis">Konstantinos Zarogoulidis</name></country><country name="Allemagne"><noRegion><name sortKey="Freitag, Lutz" sort="Freitag, Lutz" uniqKey="Freitag L" first="Lutz" last="Freitag">Lutz Freitag</name></noRegion><name sortKey="Eberhardt, Wilfried" sort="Eberhardt, Wilfried" uniqKey="Eberhardt W" first="Wilfried" last="Eberhardt">Wilfried Eberhardt</name><name sortKey="Hohenforst Schmidt, Wolfgang" sort="Hohenforst Schmidt, Wolfgang" uniqKey="Hohenforst Schmidt W" first="Wolfgang" last="Hohenforst-Schmidt">Wolfgang Hohenforst-Schmidt</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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