Gemcitabine chemotherapy induces phenotypic alterations of tumor cells that facilitate antitumor T cell responses in a mouse model of oral cancer

Kei Tomihara*, Hiroki Fuse, Wataru Heshiki, Rie Takei, Bin Zhang, Naoya Arai, Kenji Nakamori, Makoto Noguchi

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Objectives Gemcitabine (GEM) is a pyrimidine nucleoside analogue that is a new chemotherapeutic agent used for treating various cancers. Because accumulating evidence indicates that GEM may activate host immune responses, its potential as an immune modulator in cancer chemotherapy has generated considerable interest. Materials and methods In the present study, we investigated the antitumor effects of GEM using a mouse oral cancer model using immunological analyses. We examined apoptotic cell death of tumor cells with GEM treatment both in vitro and in vivo. We also investigated whether in vivo administration of GEM affected the distributions of immune cells, tumor-cell surface expression levels of immune accessory molecules and T cell immune responses in tumor-bearing mice. Results GEM induced significant oral cancer-cell apoptosis in vitro, and in vivo GEM administration markedly attenuated established mouse tumor growth. In vivo GEM administration decreased the numbers of both myeloid-derived suppressor cells (MDSCs) and B cells in tumor-bearing mice and enhanced dendritic cell maturation. Moreover, GEM treatment upregulated tumor-cell surface expressions of several immune accessory molecules and adhesion molecules, including CD80, CD86, CD40, ICAM-1, VCAM-1, and P-selectin. Remarkably, these tumor cells augmented tumor specific T-cell responses. Conclusion These results suggest that GEM can induce host antitumor immune responses, which would facilitate antitumor effects in the treatment of oral cancer.

Original languageEnglish (US)
Pages (from-to)457-467
Number of pages11
JournalOral Oncology
Volume50
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Antitumor immune response
  • Chemotherapy
  • Gemcitabine
  • Oral cancer

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Gemcitabine chemotherapy induces phenotypic alterations of tumor cells that facilitate antitumor T cell responses in a mouse model of oral cancer'. Together they form a unique fingerprint.

  • Cite this