title: Functional Alteration of Tumor-infiltrating Myeloid Cells in RNA Adjuvant Therapy.
abstract: Macrophages, as well as dendritic cells (DCs), are derived from myeloid progenitor cells. Recent evidence suggests that tumor-infiltrating macrophages differ in many aspects from conventional tissue macrophages, including nature, function and markers. Tumors usually contain various myeloid lineage cells in their non-parenchymal environment. In immunotherapy for cancer, tumor cells and non-parenchymal cells are exposed to tumor-associated antigens (TAA) and tumor-cell-derived nucleic acids. In addition, a dsRNA mimic, polyinosinic:polycytidylic acid (polyI:C), exhibits strong adjuvant activity, which acts both on the immune system and tumor constituents. Herein we discuss the RNA recognition system and unique cellular output in tumor-associated myeloid cells in response to immunotherapy. We especially focus on the mechanism by which RNA adjuvant alters the tumor-supportive nature of tumor-infiltrated myeloid cells to those with tumoricidal activity. We discuss how RNA administration makes tumor cells collapse and its significance of evoking cell death signals in tumor cells and macrophages. This knowledge will be applicable to the development of an alternative immunotherapy for cancer.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan seya-tu@pop.med.hokudai.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shime
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011070:Poly I-C / Q000276:immunology / Q000627:therapeutic use*; D012313:RNA / Q000276:immunology / Q000627:therapeutic use*; D051196:Toll-Like Receptor 3 / Q000276:immunology; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D012313:RNA; D052247:Nitric Oxide Synthase Type II; D011070:Poly I-C
keywords: Poly(I:C); TICAM-1; Toll-like receptor 3; Tumor-associated macrophages (TAM); antitumor immunotherapy; dendritic cells (DCs); myeloid-derived suppressor cells (MDSC); review