T cell dysfunction in cancer:: Role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress

T cell dysfunction characterized by a decreased T-cell proliferation and a diminished cytokine production, accompanied by the loss of CD3ζ chain, an inability to upregulate Jak-3 and translocate NFκBp65, are frequent alterations observed in the T cells of cancer patients. These alterations are likely to impair the therapeutic efficacy of immunotherapy. New findings suggest that tumor cells may induce one or more of several evasion mechanisms mediated by myeloid suppressor cells which will ultimately render the T cell anergic or tolerant. These include the depletion of the amino-acids arginine and tryptophan and the production of NO and reactive oxygen species. It is possible that some tumors can produce these factors directly. Understanding the mechanisms by which tumors impair T cell function in the different types of cancer, will be essential for developing novel approaches to block these evasion strategies, allowing the immune system to respond to cytokines, cancer vaccines or other immune stimulating therapies which could make immunotherapy a more effective form of treatment for malignancies.