Cytokine Regulation Of Immune Tolerance To Tumors

Cytokines are regulatory peptides that control virtually all physiological processes through the modulation of cell proliferation, differentiation, migration, and survival. It is a rule rather than an exception that most cytokines have pleiotropic functions and sometimes opposite influences on disease pathology, depending on their dose, timing of action, and targets. This role cannot be overemphasized when considering cytokine regulation of tumor development. The following sections focus on cytokine regulation of immune tolerance to tumors and describe their function in other aspects of tumor development.

In most cases, an effective immune response against tumors is dependent on the cellular arm of the immune system, the major players of which include CD8 + cytotoxic T lymphocytes (CTLs), CD4 + Th1 cells, y8-T cells, and NK cells. The effector functions of these cells are responsible for direct target cell killing as well as production of cytokines and other modulators that regulate the function of various cell types, including tumor cells. The cellular immune response is responsible for the host defense of intracellular pathogens; however, when the cellular immune response is dysregu-lated, it can also trigger autoimmune diseases (e.g., type I diabetes). As a self-tolerance mechanism, several cytokines are involved in the suppression of cellular immune responses either under steady state or during the resolution phase of infection or trauma, which impedes the development of tumor immunity. In addition, cytokines that skew immune responses to T helper 2 (Th2) cells or to the newly discovered Th17 pathway can also influence immune responses to tumors. Therefore, cytokine inhibition of tumor immunity can be caused by immune suppression or deviation.

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