Immunotherapy with dendritic cells directed against tumor antigens shared with normal host cells results in severe autoimmune disease

Vaccination with dendritic cells (DCs) presenting tumor antigens induces pr imary immune response or amplifies existing cytotoxic antitumor T cell resp onses. This study documents that antitumor treatment with DCs may cause sev ere autoimmune disease when the tumor antigens are not tumor-specific but a re also expressed in peripheral nonlymphoid organs. Growing tumors with suc h shared tumor antigens that were, at least initially, strictly located out side of secondary lymphoid organs were successfully controlled by specific DC vaccination. However, antitumor treatment was accompanied by fatal autoi mmune disease, i.e., autoimmune diabetes in transgenic mice expressing the tumor antigen also in pancreatic beta islet cells or by severe arteritis, m yocarditis, and eventually dilated cardiomyopathy when arterial smooth musc le cells and cardiomyocytes expressed the transgenic tumor antigen. These r esults reveal the delicate balance between tumor immunity and autoimmunity and therefore point out important limitations for the use of not strictly t umor-specific antigens in antitumor vaccination with DCs.