title: Gemcitabine chemotherapy induces phenotypic alterations of tumor cells that facilitate antitumor T cell responses in a mouse model of oral cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These results suggest that GEM can induce host antitumor immune responses, which would facilitate antitumor effects in the treatment of oral cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan. Electronic address: tomihara@med.u-toyama.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Tomihara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fuse
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Heshiki
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Takei
authors.affiliation: Department of Medicine-Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 300 E Superior Street-Tarry, 13-705, Chicago, IL 60611, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Reparative and Regenerative Medicine, Institute of Medical Science, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Arai
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamori
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Antitumor immune response; Chemotherapy; Gemcitabine; Oral cancer