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Immunotherapy has gained increasing attention as a promising anti-cancer modality over the past decade. Although immune tolerance and loss of immune surveillance have been shown to be contributing factors to tumor progression, T cells are the primary effectors of the immune system. The ability to exploit the host anti-tumor response has the potential to be clinically beneficial. Successful tumor-specific T cell activation relies on the presence of antigen, T cell receptor engagement, and costimulation. In addition to enhancing T-cell activation, recent evidence suggests that immune suppressive cells such as regulatory T cells, tolerogenic dendritic cells and myeloid derived suppressor cells have a deleterious effect on the anti-tumor response. Moreover, depleting tumor antigen-presenting cells renders the tumor cells more immunogenic to T cells. Immune modulators could be designed to target these suppressive cells to enhance tumor immunity. Although such immunomodulatory agents have shown promising results in animal models, their clinical efficacy in cancer patients remains to be proven. In this review, we discuss the rationale for developing immune modulating agents targeting the components of the immune system in the attempt to enhance the induction of anti-t
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