The hypothesis of immunologic surveillance of neoplasia is predicated on the theory that the immune system is capable of discriminating self from foreign antigens, and that tumor-specific antigens are regarded by the immune system as nonself. We propose here an alternate view, that the immune system has evolved to detect danger by employing 'professional' antigen-presenting cells as sentinels of tissue distress. In this model, cancers do not appear dangerous to the immune system, so that the default response of T cells to tumors is to be turned off. We discuss the implications for immunotherapy of malignancy.
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