Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T cell infiltration and tumor control,
Michelle Hong, Anne-Laure Puaux, Caleb Huang, et al.
Cancer Res Published OnlineFirst September 26, 2011.
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 intra-tumoral expression
of these chemokines and favored T cell infiltration into cutaneous tumors. In melanoma patients,
these chemokines were also up-regulated 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
intra-tumoral expression of chemokines as a novel cell-extrinsic mechanism of action of
chemotherapy that results in the recruitment of immune cells with anti-tumor 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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