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Cytokines are molecular mediators of intercellular signaling that function to regulate homeostasis of the immune system. There are five families of cytokines classified by their receptor usage. The effects of individual cytokines on immunity depend on several factors, including the local cytokine concentration, the pattern of cytokine receptor expression, and the integration of multiple signaling pathways in responding immune cells. Cytokines have shown therapeutic potential for the initiation and potentiation of antitumor immunity. Interferon-α and interleukin-2 (IL-2) have been approved as single agents for the treatment of metastatic melanoma and renal cell carcinoma, and several other cytokines have shown promise in preclinical tumor models. New strategies for improving the therapeutic benefit of cytokines are in development and include cytokine-antibody fusion molecules, delivery in recombinant viral vectors, expression by irradiated whole tumor cells, PEGylation, DNA vaccination, and ex vivo exposure to immune effector cells.