title: Poly (I: C) modulates the immunosuppressive activity of myeloid-derived suppressor cells in a murine model of breast cancer.
abstract: Polyinosinic-polycytidylic acid [Poly (I: C)], a ligand for Toll-like receptor (TLR-3), is used as an adjuvant to enhance anti-tumor immunity because of its prominent effects on CD8 T cells and NK cells. Myeloid-derived suppressor cells (MDSCs) are one of the main immunosuppressive factors in cancer, and their abnormal accumulation is correlated with the clinical stage of breast cancer and is an important mechanism of tumor immune evasion. Although Poly (I: C) is thought to have direct anti-tumor activity in different cell lines, its effect on immunosuppressive MDSCs in tumor-bearing animals has not been studied. 4T1-Luc, a metastatic breast cancer mouse cell line, was injected into the left flank of female BALB/c mice. Tumor-bearing mice were treated with i.p. injection of Poly (I: C) or PBS beginning on day 7 after tumor inoculation. WBCs and MDSCs were counted using coulter counter and stained for flow cytometry, respectively. Bioluminescent imaging was used to monitor tumor burden at multiple time points during the course of tumor growth. Poly (I: C) treatment led to a decrease in MDSC frequencies in BM, blood, and tumor compared to saline-treated control mice. Poly (I: C) treatment also abrogated the immunosuppressive function of MDSCs, concomitant with an increase in local T cell response of the immune system in a murine model of breast cancer. Poly (I: C) treatment decreases MDSC frequency and immunosuppressive function in 4T1-tumor-bearing hosts and effectively augments the activity of breast cancer immunotherapy.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA, pforgha@emory.edu.
authors.forename: Parvin
authors.initials: P
authors.lastname: Forghani
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D056747:Immunomodulation / Q000187:drug effects*; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D047368:Tumor Burden / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D017382:Reactive Oxygen Species; D051196:Toll-Like Receptor 3; D011070:Poly I-C