Utility of Clostridium difficile Toxin B for Inducing Anti-Tumor Immunity

作者：Huang, Tuxiong; Li, Shan; Li, Guangchao; Tian, Yuan; Wang, Haiying; Shi, Lianfa; Perez-Cordon, Gregorio; Mao, Li; Wang, Xiaoning; Wang, Jufang^*; Feng, Hanping

来源：PLos One, 2014, 9(10): e110826.

DOI：10.1371/journal.pone.0110826

• APOPTOTIC TUMOR-CELLS
• DENDRITIC CELLS
• CALRETICULIN EXPOSURE
• HUMAN MONOCYTES
• CANCER
• IMMUNOGENICITY
• INFECTION
• PROTEINS
• DEATH
• RHO

Clostridium difficile toxin B (TcdB) is a key virulence factor of bacterium and induces intestinal inflammatory disease. Because of its potent cytotoxic and proinflammatory activities, we investigated the utility of TcdB in developing anti-tumor immunity. TcdB induced cell death in mouse colorectal cancer CT26 cells, and the intoxicated cells stimulated the activation of mouse bone marrow-derived dendritic cells and subsequent T cell activation in vitro. Immunization of BALB/c mice with toxin-treated CT26 cells elicited potent anti-tumor immunity that protected mice from a lethal challenge of the same tumor cells and rejected pre-injected tumors. The anti-tumor immunity generated was cell-mediated, long-term, and tumor-specific. Further experiments demonstrated that the intact cell bodies were important for the immunogenicity since lysing the toxin-treated tumor cells reduced their ability to induce antitumor immunity. Finally, we showed that TcdB is able to induce potent anti-tumor immunity in B16-F10 melanoma model. Taken together, these data demonstrate the utility of C. difficile toxin B for developing anti-tumor immunity.

• 出版日期2014-10-23
• 单位中国人民解放军总医院; 华南理工大学