RT Journal Article
SR Electronic
T1 Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 6997
OP 7009
DO 10.1158/0008-5472.CAN-11-1466
VO 71
IS 22
A1 Hong, Michelle
A1 Puaux, Anne-Laure
A1 Huang, Caleb
A1 Loumagne, Laure
A1 Tow, Charlene
A1 Mackay, Charles
A1 Kato, Masashi
A1 Prévost-Blondel, Armelle
A1 Avril, Marie-Françoise
A1 Nardin, Alessandra
A1 Abastado, Jean-Pierre
YR 2011
UL http://cancerres.aacrjournals.org/content/71/22/6997.abstract
AB 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. Cancer Res; 71(22); 6997–7009. ©2011 AACR.