title: IFN-γ mediates graft-versus-breast cancer effects via enhancing cytotoxic T lymphocyte activity.
abstract: Previous studies have demonstrated the beneficial effect of graft-versus-tumor (GVT) following hematopoietic stem cell transplantation (HSCT) on the incidence of leukemia relapse and the overall survival rate of patients with leukemia; however, detailed mechanisms underlying the effects GVT exhibits on solid tumors following allogeneic HSCT are yet to be elucidated. The aim of the present study was to investigate the immune mechanism underlying the effect of interferon (IFN)-γ on GVT following allogeneic HSCT in breast cancer therapy. Anin situbreast cancer mouse model was established by injecting 5×1044T1 cells into the mammary fat pads of BALB/c mice. The 4T1 cells were transfected with the firefly luciferase reporter gene in order to monitor the tumor progression in real time. An allogeneic HSCT model was then established by transplanting bone marrow mononuclear cells from C57BL/6 mice to the BALB/c mice. To investigate the influence of T lymphocyte proliferation following allogeneic bone marrow transplantation, the levels of CD3+CD8+cytotoxic T lymphocytes (CTLs) and CD4+CD25+regulatory T cells were determined. In addition, IFN-γ and granzyme B expression levels in splenic lymphocytes were analyzed using flow cytometry. Allogeneic HSCT was found to significantly promote the proliferation and cytotoxicity of CTLs and suppress the growth of breast cancer. Furthermore, the secretory levels of IFN-γ and granzyme B by T cells were elevated following allogeneic HSCT. These results indicated that alloreactive T cells increased the secretion of IFN-γ, which promoted the alloresponse of donor CTLs. In addition, the CTLs produced granzyme B, which exerted a tumor suppressive effect.
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China ; Key Laboratory of Bioactive Materials, College of Life Science, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Qianjie
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Ningning
authors.initials: N
authors.lastname: He
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Leng
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Yuebing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Pathophysiology, School of Medicine, Nankai University, Ministry of Education, Tianjin 300071, P.R. China ; Key Laboratory of Bioactive Materials, College of Life Science, Nankai University, Ministry of Education, Tianjin 300071, P.R. China.
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
keywords: breast cancer; cytotoxic T lymphocytes; graft-versus-tumor; granzyme B; interferon-γ