Increase in the immunostimulatory effect of dendritic cells by pulsing with serum derived from pancreatic and colorectal cancer patients
ABSTRACT
Both we and others have observed a relative resistance of solid tumor cells to immunological effector cells in vitro, which may be one reason for the clinical phenomenon of resistance of patients with pancreatic carcinoma or other solid tumors to immunological therapeutic approaches. Dendritic cells (DC) are professional antigen-presenting cells which can process and present tumor-associated antigens such as CA 19-9. Here we tested DC pulsed with serum containing CA 19-9 for their capacity to stimulate immunological effector cells against pancreatic carcinoma cells. Coculture of immunological effector cells with DC led to a significant increase in cytotoxic activity as measured by a lactic dehydrogenase release assay. Most interestingly, cytotoxic activity against tumor cells was further increased using DC pulsed with patient-derived CA 19-9 containing serum. Similar results have been obtained using either autologous or allogeneic serum from patients with pancreas carcinoma. The effect of serum on the cytotoxicity of effector cells increased in a dose-dependent manner. Interestingly, heat inactivation led to a significant loss of immunostimulatory capacity of the serum. Cytotoxicity was partially inhibited by using an antibody directed against CA 19-9 on the surface of the target cells. Best results were obtained when adding CA 19-9 protein to CA 19-9 containing serum for pulsing of DC. In conclusion, DC pulsed with CA 19-9 containing serum increased the cytotoxic activity of immunological effector cells against pancreatic cancer cells. DC pulsed with CA 19-9 containing serum with or without additional exogenous CA 19-9 protein may have an impact on immunotherapeutic protocols for patients with CA 19-9 secreting tumors.