机构：[a]The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA[b]Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China[c]Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA[d]Center for Biostatistics, Department of Bioinformatics, The Ohio State University, Columbus, OH, USA[e]Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA[f]Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA[g]The James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
Natural products comprise an important class of biologically active molecules. Many of these compounds derived from natural sources exhibit specific physiologic or biochemical effects. An example of a natural product is chitosan, which is enriched in the shells of certain seafood that are frequently consumed worldwide. Like other natural products, chitosan has the potential for applications in clinical medicine and perhaps in cancer therapy. Toward this end, the immunomodulatory or anti-cancer properties of chitosan have yet to be reported. In this study, we discovered that chitosan enhanced the anti-tumor activity of natural killer (NK) cells by activating dendritic cells (DCs). In the presence of DCs, chitosan augmented IFN-γ production by human NK cells. Mechanistically, chitosan activated DCs to express pro-inflammatory cytokines such as interleukin (IL)-12 and IL-15, which in turn activated the STAT4 and NF-κB signaling pathways, respectively, in NK cells. Moreover, chitosan promoted NK cell survival, and also enhanced NK cell cytotoxicity against leukemia cells. Finally, a related in vivo study demonstrated that chitosan activated NK cells against B16F10 tumor cells in an immunocompetent syngeneic murine melanoma model. This effect was accompanied by in vivo upregulation of IL-12 and IL-15 in DCs, as well as increased IFN-γ production and cytolytic degranulation in NK cells. Collectively, our results demonstrate that chitosan activates DCs leading to enhanced capacity for immune surveillance by NK cells. We believe that our study has future clinical applications for chitosan in the prevention or treatment of cancer and infectious diseases.
基金：
NIH (CA185301), NIH (AI129582), NIH (NS106170), NIH (CA068458),
NIH (CA163205), the Gabrielle’s Angel Cancer Research Foundation, the
Leukemia & Lymphoma Society Transnational Research Award, and the
American Cancer Society Scholar Award (RSG-14-243-01-LIB).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|1 区医学
小类|2 区免疫学2 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|2 区免疫学2 区肿瘤学
第一作者：
第一作者机构：[a]The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA[b]Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
通讯作者：
通讯机构：[a]The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA[f]Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA[g]The James Cancer Hospital and Solove Research Institute, Columbus, OH, USA[*1]Biomedical Research Tower 816, 460 West 12th Avenue, The Ohio State University, Columbus, OH, 43210[*2]The Comprehensive Cancer Center, The James Cancer Hospital & Solove Research Institute, The Ohio State University.
推荐引用方式(GB/T 7714)：
Xinxin Li,Wenjuan Dong,Ansel P. Nalin,et al.The natural product chitosan enhances the anti-tumor activity of natural killer cells by activating dendritic cells.[J].Oncoimmunology.2018,7(6):e1431085.doi:10.1080/2162402X.2018.1431085.
APA：
Xinxin Li,Wenjuan Dong,Ansel P. Nalin,Yufeng Wang,Pan Pan...&Jianhua Yu.(2018).The natural product chitosan enhances the anti-tumor activity of natural killer cells by activating dendritic cells..Oncoimmunology,7,(6)
MLA：
Xinxin Li,et al."The natural product chitosan enhances the anti-tumor activity of natural killer cells by activating dendritic cells.".Oncoimmunology 7..6(2018):e1431085
医学