IMMUNE SURVEILLANCE - PARANEOPLASTIC OR ENVIRONMENTAL TRIGGERS OF AUTOIMMUNITY

Autoimmunity associated with tumor cell development seems an important mechanism by which to prevent progression to clinical cancer. In this brief review, tumor autoantigens associated with paraneoplastic syndr ome, non-HLA-associated organ-specific autoimmune diseases, and the hi ghly cell-specific autoimmune eradication of the islet beta cells in t ype 1 diabetes are compared and discussed. It is suggested that autore activity is important in preventing tumor formation; however, it may b e at the expense of the development of autoimmune disease. Although th e cytotoxic T lymphocytes (CTL) induction by HLA class I has been stud ied and used in clinical trials, little is understood about the initia tion and HLA class II mediated induction of an immune response to neop lastic cells. This induction apparently takes place because paraneopla stic disorders are often due to an immune response to the tumor cell r esulting in a cross-reactivity with a normally expressed autoantigen o n a remote nontumor-associated target cell. The problem of immune surv eillance to eradicate neoplasm or downregulate pathological autoimmuni ty are therefore closely related phenomena. An improved understanding of immune mediated tumor suppression should therefore greatly benefit immunotherapy of type 1 diabetes, and the two areas of research would benefit from an interdisciplinary endeavor.