Kinetics of tumor cell apoptosis and immune cell activation during the regression of tumors induced by lipid A in a rat model of colon cancer

Despite the wide range of available therapies, human colon cancers remain difficult to cure. Evidence for efficient antitumoral immune responses to be raised is now widely accepted, and numerous strategies exploiting the host immune system have been developed. A treatment based on the lipid-A derivative OM-174 has been developed in our laboratory. OM-174 induces the rejection of tumors established by injection of PROb colon cancer cells in syngeneic BDIX rats. Our immunohistochemistry study demonstrated that OM-174 treatment is associated with tumor cell apoptosis. Caspase 3 activation was detetected 24 h after the first OM-174 injection. Six days after the beginning of the treatment, dendritic cells were the first immune cells that invaded tumor nodules. When dendritic cells came into contact with apoptotic tumor cells, an increased expression of the costimulatory molecules B7-1 and B7-2 was detected at the surface of these cells. Five days later, macrophages were found in the tumor nodules. Lymphocytes organized into a crown surrounding the nodules that progressively regressed during the treatment. T lymphocytes were not in contact with tumor cells or apoptotic cells at any time point. The kinetics of tumor cell apoptosis induced by OM-174, as well as the appearance of innate followed by adaptative immune cells in the tumor nodules, were compatible with cell activation and the development of immune response.