Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control
Identifieur interne : 007127 ( Main/Merge ); précédent : 007126; suivant : 007128Chemotherapy 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.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Médicament.
English descriptors
- KwdEn :
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.
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Pascal:12-0020313Le document en format XML
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<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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