Open AccessInflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD 4+ T cells with clinical impact
Author(s) -
Komura Takuya,
Sakai Yoshio,
Harada Kenichi,
Kawaguchi Kazunori,
Takabatake Hisashi,
Kitagawa Hirohisa,
Wada Takashi,
Honda Masao,
Ohta Tetsuo,
Nakanuma Yasuni,
Kaneko Shuichi
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12663
Subject(s) - cd14 , chemokine , pancreatic cancer , immune system , monocyte , immunology , medicine , cd163 , inflammation , flow cytometry , cancer research , cytokine , cancer , biology , macrophage , in vitro , biochemistry
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 CD 33+ CD 163+ M2 macrophages and CD 4+ 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 CD 14+ monocytes and CD 4+ 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 CD 4+ T cells of PDAC patients. Correspondingly, the frequency of CD 4+ 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 CD 4+ T cells with influence of the clinical prognosis.