title: Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-γ-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis.
authors.affiliation: Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Komura
authors.affiliation: Department of Gastroenterology, Kanazawa University, Kanazawa, Japan.|Department of Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Human Pathology, Kanazawa University, Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan.|Department of Gastroenterology, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan.|Department of Gastroenterology, Kanazawa University, Kanazawa, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takabatake
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Gastroenterology, Kanazawa University, Kanazawa, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Human Pathology, Kanazawa University, Kanazawa, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan.|Department of Gastroenterology, Kanazawa University, Kanazawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis; D059467:Transcriptome
chemical_list: D018925:Chemokines; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: CD4+ T cells; macrophages; monocytes; pancreatic ductal adenocarcinoma; programmed cell death-1
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