Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T cell infiltration and tumor control
Menée in vitro et à l'aide d'un modèle murin de mélanome, cette étude identifie un mécanisme par lequel une chimiothérapie (dacarbazine, témozolomide ou cisplatine) induit l'expression intra-tumorale de chimiokines favorisant l'infiltration de lymphocytes T
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.