AustralieFrV1, Main, Exploration, bibRecordById, Pascal:12-0020313

Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control

Identifieur interne : 006C68 ( Main/Exploration ); précédent : 006C67; suivant : 006C69

Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control

Auteurs : MICHELLE HONG [Singapour] ; Anne-Laure Puaux [Singapour] ; Caleb Huang [Singapour] ; Laure Loumagne [Singapour] ; Charlene Tow [Singapour] ; Charles Mackay [Australie] ; Masashi Kato [Japon] ; Armelle Prevost-Blondel [France] ; Marie-Françoise Avril [France] ; Alessandra Nardin [Singapour] ; Jean-Pierre Abastado [Singapour]

Source :

Cancer research : (Baltimore) [ 0008-5472 ] ; 2011.

RBID : Pascal:12-0020313

Descripteurs français

Pascal (Inist)
- Chimiothérapie, Voie intratumorale, Expression génique, Chimiokine, Cancer de la peau, Lymphocyte T, Médicament, Tumeur maligne, Dacarbazine, Témozolomide, Cisplatine, In vitro, Mécanisme action, Anticancéreux.
Wicri :
- topic : Médicament.

English descriptors

KwdEn :
- Antineoplastic agent, Chemokine, Chemotherapy, Cisplatin, Dacarbazine, Drug, Gene expression, In vitro, Intratumoral administration, Malignant tumor, Mechanism of action, Skin cancer, T-Lymphocyte, Temozolomide.

Abstract

T-cell infiltration is known to impact tumor growth and is associated with cancer patient survival. However, the molecular cues that favor T-cell infiltration remain largely undefined. Here, using a genetically engineered mouse model of melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T cells into cutaneous metastases, and their expression inhibits tumor growth. Treatment of tumor-bearing mice with chemotherapy induced intratumoral expression of these chemokines and favored T-cell infiltration into cutaneous tumors. In patients with melanoma, these chemokines were also upregulated in chemotherapy-sensitive lesions following chemotherapy, and correlated with T-cell infiltration, tumor control, and patient survival. We found that dacarbazine, temozolomide, and cisplatin induced expression of T-cell-attracting chemokines in several human melanoma cell lines in vitro. These data identify the induction of intratumoral expression of chemokines as a novel cell-extrinsic mechanism of action of chemotherapy that results in the recruitment of immune cells with antitumor activity. Therefore, identifying chemotherapeutic drugs able to induce the expression of T-cell-attracting chemokines in cancer cells may represent a novel strategy to improve the efficacy of cancer immunotherapy.

Affiliations:

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Le document en format XML

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<author><name sortKey="Nardin, Alessandra" sort="Nardin, Alessandra" uniqKey="Nardin A" first="Alessandra" last="Nardin">Alessandra Nardin</name>
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<author><name sortKey="Abastado, Jean Pierre" sort="Abastado, Jean Pierre" uniqKey="Abastado J" first="Jean-Pierre" last="Abastado">Jean-Pierre Abastado</name>
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<series><title level="j" type="main">Cancer research : (Baltimore)</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term>
<term>Chemokine</term>
<term>Chemotherapy</term>
<term>Cisplatin</term>
<term>Dacarbazine</term>
<term>Drug</term>
<term>Gene expression</term>
<term>In vitro</term>
<term>Intratumoral administration</term>
<term>Malignant tumor</term>
<term>Mechanism of action</term>
<term>Skin cancer</term>
<term>T-Lymphocyte</term>
<term>Temozolomide</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Chimiothérapie</term>
<term>Voie intratumorale</term>
<term>Expression génique</term>
<term>Chimiokine</term>
<term>Cancer de la peau</term>
<term>Lymphocyte T</term>
<term>Médicament</term>
<term>Tumeur maligne</term>
<term>Dacarbazine</term>
<term>Témozolomide</term>
<term>Cisplatine</term>
<term>In vitro</term>
<term>Mécanisme action</term>
<term>Anticancéreux</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">T-cell infiltration is known to impact tumor growth and is associated with cancer patient survival. However, the molecular cues that favor T-cell infiltration remain largely undefined. Here, using a genetically engineered mouse model of melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T cells into cutaneous metastases, and their expression inhibits tumor growth. Treatment of tumor-bearing mice with chemotherapy induced intratumoral expression of these chemokines and favored T-cell infiltration into cutaneous tumors. In patients with melanoma, these chemokines were also upregulated in chemotherapy-sensitive lesions following chemotherapy, and correlated with T-cell infiltration, tumor control, and patient survival. We found that dacarbazine, temozolomide, and cisplatin induced expression of T-cell-attracting chemokines in several human melanoma cell lines in vitro. These data identify the induction of intratumoral expression of chemokines as a novel cell-extrinsic mechanism of action of chemotherapy that results in the recruitment of immune cells with antitumor activity. Therefore, identifying chemotherapeutic drugs able to induce the expression of T-cell-attracting chemokines in cancer cells may represent a novel strategy to improve the efficacy of cancer immunotherapy.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Japon</li>
<li>Singapour</li>
</country>
<region><li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
<orgName><li>Université Paris-Descartes</li>
</orgName>
</list>
<tree><country name="Singapour"><noRegion><name sortKey="Michelle Hong" sort="Michelle Hong" uniqKey="Michelle Hong" last="Michelle Hong">MICHELLE HONG</name>
</noRegion>
<name sortKey="Abastado, Jean Pierre" sort="Abastado, Jean Pierre" uniqKey="Abastado J" first="Jean-Pierre" last="Abastado">Jean-Pierre Abastado</name>
<name sortKey="Huang, Caleb" sort="Huang, Caleb" uniqKey="Huang C" first="Caleb" last="Huang">Caleb Huang</name>
<name sortKey="Loumagne, Laure" sort="Loumagne, Laure" uniqKey="Loumagne L" first="Laure" last="Loumagne">Laure Loumagne</name>
<name sortKey="Nardin, Alessandra" sort="Nardin, Alessandra" uniqKey="Nardin A" first="Alessandra" last="Nardin">Alessandra Nardin</name>
<name sortKey="Puaux, Anne Laure" sort="Puaux, Anne Laure" uniqKey="Puaux A" first="Anne-Laure" last="Puaux">Anne-Laure Puaux</name>
<name sortKey="Tow, Charlene" sort="Tow, Charlene" uniqKey="Tow C" first="Charlene" last="Tow">Charlene Tow</name>
</country>
<country name="Australie"><noRegion><name sortKey="Mackay, Charles" sort="Mackay, Charles" uniqKey="Mackay C" first="Charles" last="Mackay">Charles Mackay</name>
</noRegion>
</country>
<country name="Japon"><noRegion><name sortKey="Kato, Masashi" sort="Kato, Masashi" uniqKey="Kato M" first="Masashi" last="Kato">Masashi Kato</name>
</noRegion>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Prevost Blondel, Armelle" sort="Prevost Blondel, Armelle" uniqKey="Prevost Blondel A" first="Armelle" last="Prevost-Blondel">Armelle Prevost-Blondel</name>
</region>
<name sortKey="Avril, Marie Francoise" sort="Avril, Marie Francoise" uniqKey="Avril M" first="Marie-Françoise" last="Avril">Marie-Françoise Avril</name>
<name sortKey="Avril, Marie Francoise" sort="Avril, Marie Francoise" uniqKey="Avril M" first="Marie-Françoise" last="Avril">Marie-Françoise Avril</name>
<name sortKey="Avril, Marie Francoise" sort="Avril, Marie Francoise" uniqKey="Avril M" first="Marie-Françoise" last="Avril">Marie-Françoise Avril</name>
<name sortKey="Prevost Blondel, Armelle" sort="Prevost Blondel, Armelle" uniqKey="Prevost Blondel A" first="Armelle" last="Prevost-Blondel">Armelle Prevost-Blondel</name>
</country>
</tree>
</affiliations>
</record>

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Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control

Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control

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