title: Enhanced NK cell adoptive antitumor effects against breast cancer in vitro via blockade of the transforming growth factor-β signaling pathway.
abstract: Natural killer (NK) cells have great potential for improving cancer immunotherapy. Adoptive NK cell transfer, an adoptive immunotherapy, represents a promising nontoxic anticancer therapy. However, existing data indicate that tumor cells can effectively escape NK cell-mediated apoptosis through immunosuppressive effects in the tumor microenvironment, and the therapeutic activity of adoptive NK cell transfer is not as efficient as anticipated. Transforming growth factor-beta (TGF-β) is a potent immunosuppressant. Genetic and epigenetic events that occur during mammary tumorigenesis circumvent the tumor-suppressing activity of TGF-β, thereby permitting late-stage breast cancer cells to acquire an invasive and metastatic phenotype in response to TGF-β. To block the TGF-β signaling pathway, NK cells were genetically modified with a dominant-negative TGF-β type II receptor by optimizing electroporation using the Amaxa Nucleofector system. These genetically modified NK cells were insensitive to TGF-β and resisted the suppressive effect of TGF-β on MCF-7 breast cancer cells in vitro. Our results demonstrate that blocking the TGF-β signaling pathway to modulate the tumor microenvironment can improve the antitumor activity of adoptive NK cells in vitro, thereby providing a new rationale for the treatment of breast cancer.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Breast and Thyroid Surgery, The Third Hospital of Zhengzhou, Zhengzhou, People's Republic of China.
authors.forename: Jinyue
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Rongguo
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Si
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
keywords: adoptive immunotherapy; breast cancer; natural killer cells; transforming growth factor-beta