Format

Send to

Choose Destination
Cancer Sci. 2019 Mar;110(3):903-912. doi: 10.1111/cas.13944. Epub 2019 Feb 14.

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

Author information

1
Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
2
Disease Control and Homeostasis, College of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
3
System Biology, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan.
4
Department of General Medicine, Kanazawa University Hospital, Kanazawa, Japan.
5
Department of Nephrology, Kanazawa University Hospital, Kanazawa, Japan.

Abstract

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.

KEYWORDS:

Gr-1; anti-cancer immunity; chemotherapy; myeloid-lineage cells; pancreatic cancer

PMID:
30657234
PMCID:
PMC6398897
DOI:
10.1111/cas.13944
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center