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

137 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

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