Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact

Cancer Science

Takuya Komura⁵  Yoshio Sakai²  Kenichi Harada¹  Kazunori Kawaguchi⁵  Hisashi Takabatake⁵  Hirohisa Kitagawa³  Takashi Wada⁴  Masao Honda²  Tetsuo Ohta³  Yasuni Nakanuma¹ 

[1] Department of Human Pathology, Kanazawa University, Kanazawa, Japan;Department of Gastroenterology, Kanazawa University, Kanazawa, Japan;Department of Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa, Japan;Department of Laboratory Medicine, Kanazawa University, Kanazawa, Japan;Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan

关键词: CD4+ T cells;    macrophages;    monocytes;    pancreatic ductal adenocarcinoma;    programmed cell death‐1;   

DOI  :  10.1111/cas.12663

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.