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.
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.
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
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.
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.
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.