Open AccessDistinct chemotherapy‐associated anti‐cancer immunity by myeloid cells inhibition in murine pancreatic cancer models
Author(s) -
Sakai Yoshio,
Miyazawa Masaki,
Komura Takuya,
Yamada Takeshi,
Nasti Alessandro,
Yoshida Keiko,
Takabatake Hisashi,
Yamato Masatoshi,
Yamashita Taro,
Yamashita Tatsuya,
Mizukoshi Eishiro,
Okuzono Mai,
Ho Tuyen Thuy Bich,
Kawaguchi Kazunori,
Wada Takashi,
Honda Masao,
Kaneko Shuichi
Publication year - 2019
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.13944
Subject(s) - myeloid , pancreatic cancer , cancer research , cd8 , immune system , medicine , immunology , cancer , cytotoxic t cell , gemcitabine , biology , biochemistry , in vitro
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with an extremely poor prognosis. Chemotherapy, such as gemcitabine (GEM), is the only treatment for PDAC patients who are not suitable for radical surgical treatment; however, its anti‐tumor efficacy is limited. In this study, we investigated the host immune system response in murine PDAC models undergoing GEM treatment. We found that PDAC tumor tissues were infiltrated with a substantial number of Gr‐1+ myeloid cells and had relatively small numbers of CD4+ and CD8+ cells. In addition, there were increased numbers of myeloid cells expressing CD11b+ and Gr‐1+ in peripheral blood. When mice with PDAC tumors in the intraperitoneal cavity or liver were treated with GEM, numbers of myeloid cells in tumor tissues and in peripheral blood decreased. In contrast, numbers of CD4+ or CD8+ cells increased. In peripheral blood, the numbers of CD8+ cells expressing interferon‐gamma (IFN‐γ) were higher in GEM‐treated mice than in untreated mice. In addition, GEM treatment in combination with myeloid cell depletion further prolonged the survival of PDAC mice. The gene expression profile of peripheral blood in myeloid cell‐depleted PDAC mice treated with GEM showed biological processes related to anti‐cancer immunity, such as natural killer cell‐mediated cytotoxicity, type I IFN signaling, and co‐stimulatory signaling for T cell activation. Thus, in PDAC murine models, GEM treatment was associated with an immune response consistent with an anti‐cancer effect, and depletion of myeloid‐lineage cells played an important role in enhancing anti‐cancer immunity associated with GEM treatment.