Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control

Michelle Hong, Anne Laure Puaux, Caleb Huang, Laure Loumagne, Charlene Tow, Charles Mackay, Masashi Kato, Armelle Prévost-Blondel, Marie Françoise Avril, Alessandra Nardin, Jean Pierre Abastado

Research output: Contribution to journalArticleResearchpeer-review

116 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6997-7009
Number of pages13
JournalCancer Research
Volume71
Issue number22
DOIs
Publication statusPublished - 15 Nov 2011

Cite this

Hong, Michelle ; Puaux, Anne Laure ; Huang, Caleb ; Loumagne, Laure ; Tow, Charlene ; Mackay, Charles ; Kato, Masashi ; Prévost-Blondel, Armelle ; Avril, Marie Françoise ; Nardin, Alessandra ; Abastado, Jean Pierre. / Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. In: Cancer Research. 2011 ; Vol. 71, No. 22. pp. 6997-7009.
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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.",
author = "Michelle Hong and Puaux, {Anne Laure} and Caleb Huang and Laure Loumagne and Charlene Tow and Charles Mackay and Masashi Kato and Armelle Pr{\'e}vost-Blondel and Avril, {Marie Fran{\cc}oise} and Alessandra Nardin and Abastado, {Jean Pierre}",
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Hong, M, Puaux, AL, Huang, C, Loumagne, L, Tow, C, Mackay, C, Kato, M, Prévost-Blondel, A, Avril, MF, Nardin, A & Abastado, JP 2011, 'Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control', Cancer Research, vol. 71, no. 22, pp. 6997-7009. https://doi.org/10.1158/0008-5472.CAN-11-1466

Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. / Hong, Michelle; Puaux, Anne Laure; Huang, Caleb; Loumagne, Laure; Tow, Charlene; Mackay, Charles; Kato, Masashi; Prévost-Blondel, Armelle; Avril, Marie Françoise; Nardin, Alessandra; Abastado, Jean Pierre.

In: Cancer Research, Vol. 71, No. 22, 15.11.2011, p. 6997-7009.

Research output: Contribution to journalArticleResearchpeer-review

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