Dong Wenqian, Zhang Huafeng, Yin Xiaonan, Liu Yuying, Chen Degao, Liang Xiaoyu, Jin Xun, Lv Jiadi, Ma Jingwei, Tang Ke, Hu Zhuowei, Qin Xiaofeng, Huang Bo
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.
Oncoimmunology. 2017 Jan 19;6(3):e1282589. doi: 10.1080/2162402X.2017.1282589. eCollection 2017.
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.
利用肠道黏膜免疫来设计新的抗肿瘤疫苗接种策略仍未得到探索。肿瘤细胞衍生的微粒（T-MP）是天然生物材料，能够将肿瘤抗原和固有信号传递给树突状细胞（DC）以产生肿瘤特异性T细胞免疫。在此，我们表明通过口服疫苗接种途径的T-MP可有效进入并激活黏膜上皮，从而引发后续的抗肿瘤T细胞反应。口服T-MP对小鼠体内B16黑色素瘤和CT26结肠癌的生长产生了强大的抑制作用，这需要T细胞和DC的激活。T-MP一旦进入肠腔，主要被回肠肠上皮细胞（IEC）摄取，在那里T-MP激活NOD2及其下游的MAPK和NF-κB，导致趋化因子释放，包括来自IEC的CCL2，以吸引CD103 CD11c DC。此外，回肠IEC可将T-MP转运至基底外侧部位，在那里T-MP被那些DC捕获以交叉呈递负载的抗原内容物。阐明这些分子和细胞机制凸显了T-MP作为一种具有巨大临床应用潜力的新型抗肿瘤口服疫苗接种策略。
