title: Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control.
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.
authors.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore, Singapore.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hong
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Puaux
authors.forename: Caleb
authors.initials: C
authors.lastname: Huang
authors.forename: Laure
authors.initials: L
authors.lastname: Loumagne
authors.forename: Charlene
authors.initials: C
authors.lastname: Tow
authors.forename: Charles
authors.initials: C
authors.lastname: Mackay
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Armelle
authors.initials: A
authors.lastname: Prévost-Blondel
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nardin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
mesh_terms: D000818:Animals; D002465:Cell Movement; D018946:Chemokine CCL5 / Q000502:physiology; D054370:Chemokine CXCL9 / Q000502:physiology; D018925:Chemokines / Q000502:physiology*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*; D000077204:Temozolomide
chemical_list: D018946:Chemokine CCL5; D054370:Chemokine CXCL9; D018925:Chemokines; D003606:Dacarbazine; D000077204:Temozolomide