Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control

Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control

Cancer Research

10.1158/0008-5472.CAN-11-1466

http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008-5472.CAN-11-1466

M. Hong, A.-L. Puaux, C. Huang, L. Loumagne, C. Tow, C. Mackay, M. Kato, A. Prevost-Blondel, M.-F. Avril, A. Nardin, J.-P. Abastado

26 September 2011

Hong, M. et al. Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. Cancer Research 71, 6997 (2011).

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.

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https://oar.a-star.edu.sg/communities-collections/articles/11855

0008-5472

Singapore Immunology Network