title: Polyinosinic-polycytidylic acid limits tumor outgrowth in a mouse model of metastatic lung cancer.
abstract: Polyinosinic-polycytidylic acid (poly I:C), a TLR3 ligand, is currently being tested in human clinical trials as an adjuvant to anti-cancer vaccines and in combination with other therapies. However, little is known about its activity in established pulmonary metastasis. The aim of our study was to elucidate the effect of poly I:C (1, 10, or 100 μg/mouse) in a mouse model of B16-F10-induced metastatic lung cancer. Lung tumor growth was arrested after a single administration of poly I:C. This was associated with higher influx of mature dendritic cells (DCs), which drove toward a Th1-like, Th17-like, and cytotoxic immune environment. The interference with IFN type I receptor signaling by means of a specific mAb reversed poly I:C-mediated tumor regression due to lower presence of myeloid DCs, cytotoxic DCs (CD11c(+)CD8(+)), NKT cells, CD8(+) T cells, and Th1-like cytokines. Moreover, the adoptive transfer of poly I:C-activated bone marrow-derived DCs into tumor-bearing mice resulted in activities similar to those of the systemic administration of poly I:C on lung tumor burden. In conclusion, our data prove that poly I:C has potential anti-tumor activity in a mouse model of established pulmonary metastasis. The activation of DCs and the production of IFN type I are responsible for an effective T cytotoxic immune response against metastatic lung cancer progression after poly I:C treatment.
authors.affiliation: Department of Pharmaceutical and Biomedical Science, University of Salerno, Fisciano, Salerno 84084, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Forte
authors.forename: Alessia
authors.initials: A
authors.lastname: Rega
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000637:transplantation; D005260:Female; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011070:Poly I-C