Clostridium difficile toxin A (TcdA) is one of the main pathogenic factors released by C. difficile. Due to its potent cytotoxic and proinflammatory activities, we investigated the anti-tumor activity of TcdA. CT26 colorectal cancer cells were challenged with recombinant TcdA, and it was found that TcdA could induce apoptosis of CT26 cells. Calreticulin (CRT) exposure to the cell surface during TcdA-induced apoptosis suggested that this apoptosis may correlate with immunogenicity. Moreover, TcdA-treated apoptotic CT26 cells were highly immunogenic since they could stimulate DC activation, T-cell activation, and anti-tumor activity. Furthermore, the anti-tumor immune response generated was specific and long-term. In summary, these studies demonstrate that C difficile toxin A can induce apoptotic death of CT26 colorectal cancer cells and stimulate potent anti-tumor immunity. (C) 2012 Elsevier Inc. All rights reserved.