Tumor necrosis factor is dispensable for the success of immunogenic anticancer chemotherapy
Identifieur interne : 004422 ( Main/Exploration ); précédent : 004421; suivant : 004423Tumor necrosis factor is dispensable for the success of immunogenic anticancer chemotherapy
Auteurs : Yuting Ma [France] ; Takahiro Yamazaki [France] ; Heng Yang [France] ; Oliver Kepp [France] ; Lorenzo Galluzzi [France] ; Laurence Zitvogel [France] ; Mark J. Smyth ; Guido Kroemer [France]Source :
- Oncoimmunology [ 2162-4011 ] ; 2013.
Abstract
The antineoplastic effects of anthracyclines have been shown to rely, at least in part, on a local immune response that involves dendritic cells (DCs) and several distinct subsets of T lymphocytes. Here, we show that the administration of anthracyclines to mice bearing established neoplasms stimulates the intratumoral secretion of tumor necrosis factor α (TNFα). However, blocking the TNFα/TNF receptor (TNFR) system by three different strategies—namely, (1) neutralizing antibodies, (2) etanercept, a recombinant protein in which TNFR is fused to the constant domain of an IgG1 molecule, and (3) gene knockout—failed to negatively affect the therapeutic efficacy of anthracyclines in three distinct tumor models. In particular, TNFα-blocking strategies did not influence the antineoplastic effects of doxorubicin (a prototypic anthracycline) against MCA205 fibrosarcomas growing in C57BL/6 mice, F244 sarcomas developing in 129/Sv hosts and H2N100 mammary carcinomas arising in BALB/c mice. These findings imply that, in contrast to other cytokines (such as interleukin-1β, interleukin-17 and interferon γ), TNFα is not required for anthracyclines to elicit therapeutic anticancer immune responses.
Url:
DOI: 10.4161/onci.24786
PubMed: 23894723
PubMed Central: 3716758
Affiliations:
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Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U848; Villejuif</wicri:regionArea><wicri:noRegion>U848; Villejuif</wicri:noRegion><wicri:noRegion>U848; Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Institut Gustave Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris</wicri:regionArea></affiliation></author><author><name sortKey="Yamazaki, Takahiro" sort="Yamazaki, Takahiro" uniqKey="Yamazaki T" first="Takahiro" last="Yamazaki">Takahiro Yamazaki</name><affiliation wicri:level="1"><nlm:aff id="A2">Institut Gustave Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">INSERM, U1015; CICBT507; Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1015; CICBT507; Villejuif</wicri:regionArea><wicri:noRegion>U1015; CICBT507; Villejuif</wicri:noRegion><wicri:noRegion>U1015; CICBT507; Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Heng" sort="Yang, Heng" uniqKey="Yang H" first="Heng" last="Yang">Heng Yang</name><affiliation wicri:level="1"><nlm:aff id="A3">Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">INSERM, UMR 996; LabEx LERMIT; Clamart, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR 996; LabEx LERMIT; Clamart</wicri:regionArea><wicri:noRegion>UMR 996; LabEx LERMIT; Clamart</wicri:noRegion><wicri:noRegion>UMR 996; LabEx LERMIT; Clamart</wicri:noRegion></affiliation></author><author><name sortKey="Kepp, Oliver" sort="Kepp, Oliver" uniqKey="Kepp O" first="Oliver" last="Kepp">Oliver Kepp</name><affiliation wicri:level="1"><nlm:aff id="A1">INSERM, U848; Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U848; Villejuif</wicri:regionArea><wicri:noRegion>U848; Villejuif</wicri:noRegion><wicri:noRegion>U848; Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Institut Gustave Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris</wicri:regionArea></affiliation></author><author><name sortKey="Galluzzi, Lorenzo" sort="Galluzzi, Lorenzo" uniqKey="Galluzzi L" first="Lorenzo" last="Galluzzi">Lorenzo Galluzzi</name><affiliation wicri:level="1"><nlm:aff id="A2">Institut Gustave Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A7">Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris</wicri:regionArea><wicri:noRegion>Centre de Recherche des Cordeliers; Paris</wicri:noRegion><wicri:noRegion>Centre de Recherche des Cordeliers; Paris</wicri:noRegion></affiliation></author><author><name sortKey="Zitvogel, Laurence" sort="Zitvogel, Laurence" uniqKey="Zitvogel L" first="Laurence" last="Zitvogel">Laurence Zitvogel</name><affiliation wicri:level="1"><nlm:aff id="A2">Institut Gustave Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">INSERM, U1015; CICBT507; Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1015; CICBT507; Villejuif</wicri:regionArea><wicri:noRegion>U1015; CICBT507; Villejuif</wicri:noRegion><wicri:noRegion>U1015; CICBT507; Villejuif</wicri:noRegion></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><nlm:aff id="A8">Cancer Immunology Program, Peter MacCallum Cancer Centre; East Melbourne, VIC Australia</nlm:aff><wicri:noCountry code="subfield">VIC Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="A9">Immunology in Cancer and Infection Laboratory, Queensland Institute of Medical Research; Herston, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="A10">School of Medicine, University of Queensland; Herston, QLD Australia</nlm:aff><wicri:noCountry code="subfield">QLD Australia</wicri:noCountry></affiliation></author><author><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name><affiliation wicri:level="1"><nlm:aff id="A1">INSERM, U848; Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U848; Villejuif</wicri:regionArea><wicri:noRegion>U848; Villejuif</wicri:noRegion><wicri:noRegion>U848; Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A7">Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris</wicri:regionArea><wicri:noRegion>Centre de Recherche des Cordeliers; Paris</wicri:noRegion><wicri:noRegion>Centre de Recherche des Cordeliers; Paris</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A11">Metabolomics and Cell Biology Platforms, Institut Gustave Roussy; Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Metabolomics and Cell Biology Platforms, Institut Gustave Roussy; Villejuif</wicri:regionArea><wicri:noRegion>Institut Gustave Roussy; Villejuif</wicri:noRegion><wicri:noRegion>Institut Gustave Roussy; Villejuif</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A12">Pôle de Biologie, Hôpital Européen Georges Pompidou; Assistance Publique-Hôpitaux de Paris; Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pôle de Biologie, Hôpital Européen Georges Pompidou; Assistance Publique-Hôpitaux de Paris; Paris</wicri:regionArea><wicri:noRegion>Hôpital Européen Georges Pompidou; Assistance Publique-Hôpitaux de Paris; Paris</wicri:noRegion><wicri:noRegion>Hôpital Européen Georges Pompidou; Assistance Publique-Hôpitaux de Paris; Paris</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncoimmunology</title><idno type="ISSN">2162-4011</idno><idno type="eISSN">2162-402X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The antineoplastic effects of anthracyclines have been shown to rely, at least in part, on a local immune response that involves dendritic cells (DCs) and several distinct subsets of T lymphocytes. Here, we show that the administration of anthracyclines to mice bearing established neoplasms stimulates the intratumoral secretion of tumor necrosis factor α (TNFα). However, blocking the TNFα/TNF receptor (TNFR) system by three different strategies—namely, (1) neutralizing antibodies, (2) etanercept, a recombinant protein in which TNFR is fused to the constant domain of an IgG<sub>1</sub> molecule, and (3) gene knockout—failed to negatively affect the therapeutic efficacy of anthracyclines in three distinct tumor models. In particular, TNFα-blocking strategies did not influence the antineoplastic effects of doxorubicin (a prototypic anthracycline) against MCA205 fibrosarcomas growing in C57BL/6 mice, F244 sarcomas developing in 129/Sv hosts and H2N100 mammary carcinomas arising in BALB/c mice. These findings imply that, in contrast to other cytokines (such as interleukin-1β, interleukin-17 and interferon γ), TNFα is not required for anthracyclines to elicit therapeutic anticancer immune responses.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Galluzzi, L" uniqKey="Galluzzi L">L Galluzzi</name></author><author><name sortKey="Senovilla, L" uniqKey="Senovilla L">L Senovilla</name></author><author><name sortKey="Zitvogel, L" uniqKey="Zitvogel L">L Zitvogel</name></author><author><name sortKey="Kroemer, G" uniqKey="Kroemer G">G Kroemer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zitvogel, L" uniqKey="Zitvogel L">L Zitvogel</name></author><author><name sortKey="Kepp, O" uniqKey="Kepp O">O Kepp</name></author><author><name sortKey="Kroemer, G" uniqKey="Kroemer G">G Kroemer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Galluzzi, L" uniqKey="Galluzzi 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M">M Held</name></author><author><name sortKey="Guizetti, J" uniqKey="Guizetti J">J Guizetti</name></author><author><name sortKey="Maar, S" uniqKey="Maar S">S Maar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Korner, H" uniqKey="Korner H">H Körner</name></author><author><name sortKey="Riminton, Ds" uniqKey="Riminton D">DS Riminton</name></author><author><name sortKey="Strickland, Dh" uniqKey="Strickland D">DH Strickland</name></author><author><name sortKey="Lemckert, Fa" uniqKey="Lemckert F">FA Lemckert</name></author><author><name sortKey="Pollard, Jd" uniqKey="Pollard J">JD Pollard</name></author><author><name sortKey="Sedgwick, Jd" uniqKey="Sedgwick J">JD Sedgwick</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name></noCountry><country name="France"><noRegion><name sortKey="Ma, Yuting" sort="Ma, Yuting" uniqKey="Ma Y" first="Yuting" last="Ma">Yuting Ma</name></noRegion><name sortKey="Galluzzi, Lorenzo" sort="Galluzzi, Lorenzo" uniqKey="Galluzzi L" first="Lorenzo" last="Galluzzi">Lorenzo Galluzzi</name><name sortKey="Galluzzi, Lorenzo" sort="Galluzzi, Lorenzo" uniqKey="Galluzzi L" first="Lorenzo" last="Galluzzi">Lorenzo Galluzzi</name><name sortKey="Galluzzi, Lorenzo" sort="Galluzzi, Lorenzo" uniqKey="Galluzzi L" first="Lorenzo" last="Galluzzi">Lorenzo Galluzzi</name><name sortKey="Kepp, Oliver" sort="Kepp, Oliver" uniqKey="Kepp O" first="Oliver" last="Kepp">Oliver Kepp</name><name sortKey="Kepp, Oliver" sort="Kepp, Oliver" uniqKey="Kepp O" first="Oliver" last="Kepp">Oliver Kepp</name><name sortKey="Kepp, Oliver" sort="Kepp, Oliver" uniqKey="Kepp O" first="Oliver" last="Kepp">Oliver Kepp</name><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name><name sortKey="Ma, Yuting" sort="Ma, Yuting" uniqKey="Ma Y" first="Yuting" last="Ma">Yuting Ma</name><name sortKey="Ma, Yuting" sort="Ma, Yuting" uniqKey="Ma Y" first="Yuting" last="Ma">Yuting Ma</name><name sortKey="Yamazaki, Takahiro" sort="Yamazaki, Takahiro" uniqKey="Yamazaki T" first="Takahiro" last="Yamazaki">Takahiro Yamazaki</name><name sortKey="Yamazaki, Takahiro" sort="Yamazaki, Takahiro" uniqKey="Yamazaki T" first="Takahiro" last="Yamazaki">Takahiro Yamazaki</name><name sortKey="Yamazaki, Takahiro" sort="Yamazaki, Takahiro" uniqKey="Yamazaki T" first="Takahiro" last="Yamazaki">Takahiro Yamazaki</name><name sortKey="Yang, Heng" sort="Yang, Heng" uniqKey="Yang H" first="Heng" last="Yang">Heng Yang</name><name sortKey="Yang, Heng" sort="Yang, Heng" uniqKey="Yang H" first="Heng" last="Yang">Heng Yang</name><name sortKey="Zitvogel, Laurence" sort="Zitvogel, Laurence" uniqKey="Zitvogel L" first="Laurence" last="Zitvogel">Laurence Zitvogel</name><name sortKey="Zitvogel, Laurence" sort="Zitvogel, Laurence" uniqKey="Zitvogel L" first="Laurence" last="Zitvogel">Laurence Zitvogel</name><name sortKey="Zitvogel, Laurence" sort="Zitvogel, Laurence" uniqKey="Zitvogel L" first="Laurence" last="Zitvogel">Laurence Zitvogel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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