Kei Tomihara1, Hiroki Fuse2, Wataru Heshiki2, Rie Takei2, Bin Zhang3, Naoya Arai4, Kenji Nakamori2, Makoto Noguchi2. 1. 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. 2. 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. 3. 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. 4. 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.
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.
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 mouseoral 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 mousetumor 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.
Authors: Hassan Iqbal; Arif Jamshed; Abu Bakar Hafeez Bhatti; Raza Hussain; Sarah Jamshed; Muhammad Irfan; Natasha Hameed; Adeel Illyas Journal: Biomed Res Int Date: 2015-05-14 Impact factor: 3.411
Authors: Nikoleta Bizymi; Sunčica Bjelica; Astrid Olsnes Kittang; Slavko Mojsilovic; Maria Velegraki; Charalampos Pontikoglou; Mikael Roussel; Elisabeth Ersvær; Juan Francisco Santibañez; Marie Lipoldová; Helen A Papadaki Journal: Hemasphere Date: 2019-01-28