Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control
Identifieur interne : 004786 ( PascalFrancis/Curation ); précédent : 004785; suivant : 004787Chemotherapy 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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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term>
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<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>
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<term>Temozolomide</term>
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<term>Cancer de la peau</term>
<term>Lymphocyte T</term>
<term>Médicament</term>
<term>Tumeur maligne</term>
<term>Dacarbazine</term>
<term>Témozolomide</term>
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<term>In vitro</term>
<term>Mécanisme action</term>
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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>
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<s3>FRA</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</fA14>
<fA20><s1>6997-7009</s1>
</fA20>
<fA21><s1>2011</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>5088</s2>
<s5>354000507350680100</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2012 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>37 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>12-0020313</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Cancer research : (Baltimore)</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02R</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B04</s0>
</fC02>
<fC02 i1="03" i2="X"><s0>002B08A</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Chimiothérapie</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Chemotherapy</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Quimioterapia</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Voie intratumorale</s0>
<s5>03</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Intratumoral administration</s0>
<s5>03</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Vía intratumoral</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Expression génique</s0>
<s5>04</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Gene expression</s0>
<s5>04</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Expresión genética</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Chimiokine</s0>
<s5>05</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Chemokine</s0>
<s5>05</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Quimioquina</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Cancer de la peau</s0>
<s2>NM</s2>
<s5>06</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Skin cancer</s0>
<s2>NM</s2>
<s5>06</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Cáncer de piel</s0>
<s2>NM</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Lymphocyte T</s0>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>T-Lymphocyte</s0>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Linfocito T</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Médicament</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Drug</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Medicamento</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Malignant tumor</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Tumor maligno</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Dacarbazine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Dacarbazine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Dacarbazina</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Témozolomide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Temozolomide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Temozolomida</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Cisplatine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Cisplatin</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Cisplatino</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>In vitro</s0>
<s5>13</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>In vitro</s0>
<s5>13</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>In vitro</s0>
<s5>13</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Mécanisme action</s0>
<s5>14</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG"><s0>Mechanism of action</s0>
<s5>14</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA"><s0>Mecanismo acción</s0>
<s5>14</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Anticancéreux</s0>
<s5>23</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Antineoplastic agent</s0>
<s5>23</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Anticanceroso</s0>
<s5>23</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Traitement</s0>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Treatment</s0>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Tratamiento</s0>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Cáncer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Pathologie de la peau</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Skin disease</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Piel patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Agent alkylant</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Alkylating agent</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Agente alquilante</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Platine II Complexe</s0>
<s2>NC</s2>
<s2>NA</s2>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Platinum II Complexes</s0>
<s2>NC</s2>
<s2>NA</s2>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Platino II Complejo</s0>
<s2>NC</s2>
<s2>NA</s2>
<s5>39</s5>
</fC07>
<fN21><s1>009</s1>
</fN21>
</pA>
</standard>
</inist>
</record>
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