title: The desmoplastic stroma plays an essential role in the accumulation and modulation of infiltrated immune cells in pancreatic adenocarcinoma.
abstract: Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGFβ, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients.
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. vegard.tjomsland@liu.se
authors.forename: Vegard
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Lina
authors.initials: L
authors.lastname: Niklasson
authors.forename: Per
authors.initials: P
authors.lastname: Sandström
authors.forename: Kurt
authors.initials: K
authors.lastname: Borch
authors.forename: Henrik
authors.initials: H
authors.lastname: Druid
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bratthäll
authors.forename: Davorka
authors.initials: D
authors.lastname: Messmer
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.forename: Anna
authors.initials: A
authors.lastname: Spångeus
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D011956:Receptors, Cell Surface / Q000378:metabolism; D017154:Stromal Cells; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D011956:Receptors, Cell Surface