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Tumor development is frequently accompanied by the immune response against "self" and altered antigens expressed by tumor cells, because these antigens on vertebrate tumors are the most prevalent molecules recognized by the immune system (18,19). This reflects the fact that tumor arise from the hosts' own tissues, and are not truly "foreign", except in the cases when tumor cells express the so-called fusion proteins and/or viral peptides. Thus, in some respects, the immune recognition of tumor appears to be different from the immune recognition of bacteria, and typically more akin to auto-immunity. In addition, the immune reaction to virally infected cells showing no malignant alterations, displays some characteristics of auto-immune reaction. This inevitably activates the regulatory mechanisms which prevent a complete destruction of tissues and organs. From these reasons, the recognitio of "self" antigens on tumor cells in most circumstances presents problems for the host immune system. First, the immunity to tumor may not develop because all vertebrates pass across the embryonic phase of establishing of specific immune tolerance on "self" molecules. Second, even when the immune system can recognize and respond to tumor antigens, immunity may not be sufficient to reject cancers, due to the activation of the mechanisms which control auto-immunity. Finally, if immunity to "self"-tumor antigens develops, there are potential auto-immune sequelae, which may also result in the activation of the control suppressor/modulatory mechanisms of the immune reaction. <p> Auto-antibodies specific to different "self" molecules have been found in the sera of tumor bearers, which could be taken as an evidence for frequent joint activity of anti-tumor immunity and autoimmunity. This emphasizes the idea that tumor patients can mount tumor immunity which could be, in part, auto-immunity. In contrast to patients with auto-immune diseases, in the majority, if not all, tumor patients the immune system is unable to combat tumor growth. </p> <p> Tumors seem to find ways to generate tolerance in the immune system by activating the control mechanisms of auto-immune reaction responsible for the tolerance against "self" molecules. These mechanisms include a down-regulation of MHC class I molecules and cellular constituents involved in the antigen processing and presentation pathways (20). Tumors can also induce several different biochemical defects in physiology of T lymphocytes. In addition, the immune response against tumors is hindered by the functional hierarchy in the immunogenicity of T and B cell determinants, abnormalities occurring in the communication between the cells of innate and adoptive immunity, as well as the inadequate cytokine network (21). </p> In line with Burnett's theory of clonal selection, T-cell clones specific to dominant determinants of tumor antigens are probably deleted during embryonic development in the process of negative selection. This could possibly continue into an adult stage as a central (thymic) deletion of tumor-specific clones, or even as a peripheral deletion in the course of extrathymic lymphocyte maturation (22). Thus, most of the tumor determinants are expected to be immunologically silent; hence effective tumor immunity cannot be induced via "self"-vaccination. Additionally, as tumor accumulates antigens during transformation they also gradually induce tolerance in T cells against these antigens. <p> Notwithstanding these and other escape mechanisms, in few cancer patients a spontaneous regression of malignant tumors was observed (23,24). Data about potential coupling of auto-antibodies and prolonged/sustained survival or even spontaneous tumor regression corroborate the previous observation. Breast cancer patients with a natural humoral response to MUC-1 and/or hsp90 exhibited a better outcome (25,26). Similar to immunological events in some auto-immune diseases, tumor in regression exhibited mainly a Th1 type response, as well as non-pathogenic auto-antibodies, but thus the form of auto-immunity did not always develop into the auto-immune disease. There is data that about the potential coupling of tumor immunity with auto-immunity has been suggested by the clinical observation that the patients with metastatic melanoma who develop vitiligo have a better prognosis (27). In addition, there are observations that support a possible protective role for the auto-immune diseases in cancer patients. In this respect, the mortality rate of cancer patients with multiple sclerosis was found to be significantly lower than that of cancer patients in general (23). This could be associated with the activation of control anti-auto-immune mechanisms which may also inhibit auto-immunity and anti-tumor activity of the immune system. </p> <p> In conclusion, the potential coupling of tumor immunity with auto-immunity has been suggested by the clinical observation that patients with metastatic tumor who develop auto-immune phenomena have a better prognosis and are more likely to respond to therapy (27,28). The differences in mechanisms underlying tumor immunity and auto-immunity could be a consequence of fundamental differences in effector mechanisms used to kill tumor cells versus normal cells. At the same time, the mechanisms controlling "self"-destructive immune reaction might be one of the important factors of anti-tumor immunity failure. </p>
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