Distinct chemotherapy-associated anti-cancer immunity by myeloid cells inhibition in murine pancreatic cancer models

Autor: Keiko Yoshida, Takashi Wada, Masatoshi Yamato, Mai Okuzono, Yoshio Sakai, Eishiro Mizukoshi, Taro Yamashita, Tuyen Thuy Bich Ho, Masaki Miyazawa, Alessandro Nasti, Masao Honda, Takuya Komura, Tatsuya Yamashita, Kazunori Kawaguchi, Hisashi Takabatake, Shuichi Kaneko, Takeshi Yamada
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Cancer Research
Myeloid
endocrine system diseases
medicine.medical_treatment
pancreatic cancer
Cell
CD8-Positive T-Lymphocytes
chemotherapy
Deoxycytidine
Mice
Basic and Clinical Immunology
0302 clinical medicine
Myeloid Cells
General Medicine
anti‐cancer immunity
Killer Cells
Natural
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Interferon Type I
Original Article
Carcinoma
Pancreatic Ductal
Antimetabolites
Antineoplastic
Gr‐1
T cell
03 medical and health sciences
Immune system
Immunity
Cell Line
Tumor
Pancreatic cancer
medicine
Animals
Humans
myeloid‐lineage cells
Chemotherapy
business.industry
Original Articles
medicine.disease
Xenograft Model Antitumor Assays
Gemcitabine
Mice
Inbred C57BL
Pancreatic Neoplasms
Disease Models
Animal
030104 developmental biology
Cancer research
Transcriptome
business
CD8
Zdroj: Cancer Science
ISSN: 1347-9032
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: