Not all malignant cells progress to invasive cancer, some may even regress, but the early detection of abnormal cells can be crucial for patient survival. Immune surveillance mechanisms are complex and provide continuous efforts for the removal of transformed cells. Naturally occurring antibodies are frontier soldiers that act as the first line of defense in the battle against cancer. During the process of carcinogenesis naturally occurring antibody responses to tumor antigens were found to be associated with improved survival and protection against the spread of cancer. Using the human hybridoma technology, a series of tumor-binding antibodies can be isolated as they have several common features: they are germ-line coded IgM antibodies, they bind to various tumor-antigens, they induce apoptosis of malignant cells, and most importantly they detect not only malignant cells but also the precursor stages (i.e., autoantigens). Natural protective autoantibodies against tumor-antigens were isolated from patients and healthy donors reflecting the development of naturally occurring B-cell responses during the process of cancer evolvement. They fulfill the definition of autoantibodies since they are self-reactive and they also bind altered self-antigens such as tumor cells. In this regard various autoantibodies such as anti-dsDNA and anti-Fas autoantibodies were found to be significantly higher in patients with various carcinomas, thus playing a role for their improved survival. Targeting T-regulatory cells, namely the expression of CTLA-4 was also found to improve survival in cancer patients. Autoimmunity and malignancy frequently coexist and they may share etiological and pathological mechanisms. Therefore, the efficacy of intravenous immunoglobulins or CTLA-4 blockade was also employed as a treatment for prevention of malignancy and metastases spread.

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