Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.
Identifieur interne : 001C98 ( Main/Curation ); précédent : 001C97; suivant : 001C99Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.
Auteurs : Deepak Mittal [Australie] ; Franco Caramia [Australie] ; Stefan Michiels [France] ; Heikki Joensuu [Finlande] ; Pirkko-Liisa Kellokumpu-Lehtinen [Finlande] ; Christos Sotiriou [Belgique] ; Sherene Loi [Australie] ; Mark J. Smyth [Australie]Source :
- Cancer research [ 1538-7445 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Femelle, Humains, Interleukines (génétique), Lignée cellulaire tumorale, Lymphocytes T CD8+ (immunologie), Récepteur ErbB-2 (génétique), Récepteur ErbB-2 (métabolisme), Souris, Souris de lignée BALB C, Survie sans rechute, Transduction du signal, Tumeurs du sein (anatomopathologie), Tumeurs du sein (génétique).
- MESH :
- anatomopathologie : Tumeurs du sein.
- génétique : Interleukines, Récepteur ErbB-2, Tumeurs du sein.
- immunologie : Lymphocytes T CD8+.
- métabolisme : Récepteur ErbB-2.
- Animaux, Femelle, Humains, Lignée cellulaire tumorale, Souris, Souris de lignée BALB C, Survie sans rechute, Transduction du signal.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Interleukins, Receptor, ErbB-2.
- genetics : Breast Neoplasms.
- immunology : CD8-Positive T-Lymphocytes.
- chemical , metabolism : Receptor, ErbB-2.
- pathology : Breast Neoplasms.
- Animals, Cell Line, Tumor, Disease-Free Survival, Female, Humans, Mice, Mice, Inbred BALB C, Signal Transduction.
Abstract
The HER2/ErbB2 monoclonal antibody (mAb) trastuzumab is combined with chemotherapy as a standard-of-care for newly diagnosed HER2(+) breast cancer patients, but some patients treated with this combination therapy experience early relapse. Our analysis of data from a clinical trial evaluating the efficacy of chemotherapy plus/minus trastuzumab suggested that the magnitude of trastuzumab benefit on distant disease-free survival was higher for increasing expression of the IL21 receptor (IL21R). Therefore, we investigated a possible role for IL21 signaling in promoting HER2 mAb therapeutic efficacy. We found that IL21R-deficient mice and wild-type mice treated with a neutralizing anti-IL21 mAb were less susceptible to trastuzumab-like anti-ErbB2 therapy. Furthermore, IL21R expression on CD8(+) T cells, but not on natural killer cells, was required for optimal anti-ErbB2 mAb efficacy, and IL21 expression was enhanced in tumor-infiltrating CD4(+) T lymphocytes after anti-ErbB2 therapy. Finally, we found that administering recombinant IL21 in combination with anti-ErbB2 therapy was therapeutic against primary tumors and experimental metastases in mice. Collectively, our findings suggest that elevating IL21 signaling may enhance trastuzumab efficacy, thus constituting a novel candidate strategy to overcome trastuzumab resistance and improve patient survival. Cancer
DOI: 10.1158/0008-5472.CAN-15-1567
PubMed: 26744522
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :002370
- to stream PubMed, to step Curation: Pour aller vers cette notice dans l'étape Curation :002338
- to stream PubMed, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :002338
- to stream Ncbi, to step Merge: Pour aller vers cette notice dans l'étape Curation :002F61
- to stream Ncbi, to step Curation: Pour aller vers cette notice dans l'étape Curation :002F61
- to stream Ncbi, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :002F61
- to stream Main, to step Merge: Pour aller vers cette notice dans l'étape Curation :001C95
Links to Exploration step
pubmed:26744522Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.</title><author><name sortKey="Mittal, Deepak" sort="Mittal, Deepak" uniqKey="Mittal D" first="Deepak" last="Mittal">Deepak Mittal</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Caramia, Franco" sort="Caramia, Franco" uniqKey="Caramia F" first="Franco" last="Caramia">Franco Caramia</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name><affiliation wicri:level="4"><nlm:affiliation>Service de Biostatistique et d'Epidemiologie, Gustave Roussy, Villejuif, France. INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biostatistique et d'Epidemiologie, Gustave Roussy, Villejuif, France. INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Joensuu, Heikki" sort="Joensuu, Heikki" uniqKey="Joensuu H" first="Heikki" last="Joensuu">Heikki Joensuu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Helsinki University Central Hospital and Helsinki University, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Oncology, Helsinki University Central Hospital and Helsinki University, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Kellokumpu Lehtinen, Pirkko Liisa" sort="Kellokumpu Lehtinen, Pirkko Liisa" uniqKey="Kellokumpu Lehtinen P" first="Pirkko-Liisa" last="Kellokumpu-Lehtinen">Pirkko-Liisa Kellokumpu-Lehtinen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Tampere University Hospital and Tampere University, Tampere, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Oncology, Tampere University Hospital and Tampere University, Tampere</wicri:regionArea><wicri:noRegion>Tampere</wicri:noRegion></affiliation></author><author><name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name><affiliation wicri:level="4"><nlm:affiliation>Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region><settlement type="city">Bruxelles</settlement></placeName><orgName type="university">Université libre de Bruxelles</orgName></affiliation></author><author><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland, Australia. Mark.Smyth@qimrberghofer.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26744522</idno><idno type="pmid">26744522</idno><idno type="doi">10.1158/0008-5472.CAN-15-1567</idno><idno type="wicri:Area/PubMed/Corpus">002370</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002370</idno><idno type="wicri:Area/PubMed/Curation">002338</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002338</idno><idno type="wicri:Area/PubMed/Checkpoint">002338</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002338</idno><idno type="wicri:Area/Ncbi/Merge">002F61</idno><idno type="wicri:Area/Ncbi/Curation">002F61</idno><idno type="wicri:Area/Ncbi/Checkpoint">002F61</idno><idno type="wicri:Area/Main/Merge">001C95</idno><idno type="wicri:Area/Main/Curation">001C98</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.</title><author><name sortKey="Mittal, Deepak" sort="Mittal, Deepak" uniqKey="Mittal D" first="Deepak" last="Mittal">Deepak Mittal</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Caramia, Franco" sort="Caramia, Franco" uniqKey="Caramia F" first="Franco" last="Caramia">Franco Caramia</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name><affiliation wicri:level="4"><nlm:affiliation>Service de Biostatistique et d'Epidemiologie, Gustave Roussy, Villejuif, France. INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biostatistique et d'Epidemiologie, Gustave Roussy, Villejuif, France. INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Joensuu, Heikki" sort="Joensuu, Heikki" uniqKey="Joensuu H" first="Heikki" last="Joensuu">Heikki Joensuu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Helsinki University Central Hospital and Helsinki University, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Oncology, Helsinki University Central Hospital and Helsinki University, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Kellokumpu Lehtinen, Pirkko Liisa" sort="Kellokumpu Lehtinen, Pirkko Liisa" uniqKey="Kellokumpu Lehtinen P" first="Pirkko-Liisa" last="Kellokumpu-Lehtinen">Pirkko-Liisa Kellokumpu-Lehtinen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Tampere University Hospital and Tampere University, Tampere, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Oncology, Tampere University Hospital and Tampere University, Tampere</wicri:regionArea><wicri:noRegion>Tampere</wicri:noRegion></affiliation></author><author><name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name><affiliation wicri:level="4"><nlm:affiliation>Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region><settlement type="city">Bruxelles</settlement></placeName><orgName type="university">Université libre de Bruxelles</orgName></affiliation></author><author><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland, Australia. Mark.Smyth@qimrberghofer.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. School of Medicine, University of Queensland, Herston, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cancer research</title><idno type="eISSN">1538-7445</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Breast Neoplasms (genetics)</term><term>Breast Neoplasms (pathology)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cell Line, Tumor</term><term>Disease-Free Survival</term><term>Female</term><term>Humans</term><term>Interleukins (genetics)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Receptor, ErbB-2 (genetics)</term><term>Receptor, ErbB-2 (metabolism)</term><term>Signal Transduction</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Interleukines (génétique)</term><term>Lignée cellulaire tumorale</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Récepteur ErbB-2 (génétique)</term><term>Récepteur ErbB-2 (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Survie sans rechute</term><term>Transduction du signal</term><term>Tumeurs du sein (anatomopathologie)</term><term>Tumeurs du sein (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukins</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interleukines</term><term>Récepteur ErbB-2</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T CD8+</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Récepteur ErbB-2</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Disease-Free Survival</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Survie sans rechute</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The HER2/ErbB2 monoclonal antibody (mAb) trastuzumab is combined with chemotherapy as a standard-of-care for newly diagnosed HER2(+) breast cancer patients, but some patients treated with this combination therapy experience early relapse. Our analysis of data from a clinical trial evaluating the efficacy of chemotherapy plus/minus trastuzumab suggested that the magnitude of trastuzumab benefit on distant disease-free survival was higher for increasing expression of the IL21 receptor (IL21R). Therefore, we investigated a possible role for IL21 signaling in promoting HER2 mAb therapeutic efficacy. We found that IL21R-deficient mice and wild-type mice treated with a neutralizing anti-IL21 mAb were less susceptible to trastuzumab-like anti-ErbB2 therapy. Furthermore, IL21R expression on CD8(+) T cells, but not on natural killer cells, was required for optimal anti-ErbB2 mAb efficacy, and IL21 expression was enhanced in tumor-infiltrating CD4(+) T lymphocytes after anti-ErbB2 therapy. Finally, we found that administering recombinant IL21 in combination with anti-ErbB2 therapy was therapeutic against primary tumors and experimental metastases in mice. Collectively, our findings suggest that elevating IL21 signaling may enhance trastuzumab efficacy, thus constituting a novel candidate strategy to overcome trastuzumab resistance and improve patient survival. Cancer</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001C98 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Curation/biblio.hfd -nk 001C98 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Curation
|type= RBID
|clé= pubmed:26744522
|texte= Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Curation/RBID.i -Sk "pubmed:26744522" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Curation/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |