title: Oral delivery of tumor microparticle vaccines activates NOD2 signaling pathway in ileac epithelium rendering potent antitumor T cell immunity.
abstract: Exploiting gut mucosal immunity to design new antitumor vaccination strategy remains unexplored. Tumor cell-derived microparticles (T-MP) are natural biomaterials that are capable of delivering tumor antigens and innate signals to dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs by oral vaccination route effectively access and activate mucosal epithelium, leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs generated potent inhibitory effect against the growth of B16 melanoma and CT26 colon cancer in mice, which required both T cell and DC activation. T-MPs, once entering intestinal lumen, were mainly taken up by ileac intestinal epithelial cells (IEC), where T-MPs activated NOD2 and its downstream MAPK and NF-κB, leading to chemokine releasing, including CCL2, from IECs to attract CD103+CD11c+DCs. Furthermore, ileac IECs could transcytose T-MPs to the basolateral site, where T-MPs were captured by those DCs for cross-presentation of loaded antigen contents. Elucidating these molecular and cellular mechanisms highlights T-MPs as a novel antitumor oral vaccination strategy with great potential of clinical applications.
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology , Wuhan, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Degao
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology , Wuhan, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology , Wuhan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: Molecular Immunology and Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing, China.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China; Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
keywords: Antitumor immunity; NOD2 signaling; intestinal epithelial cells; oral vaccines; tumor microparticles