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Dysfunction of the host immune system can be detected in many patients with different cancer types, and contributes to tumor escape and failure of therapies that aim to elicit or boost anti-tumor immunity. Yet, immune-mediated tumor rejection and long term cancer control have been documented in a minority of patients. A better understanding of immune dysfunction in the cancer bearing state and the immune mechanisms that lead to tumor rejection will enable design of novel therapeutic approaches to overcome cancer-induced immune dysfunction and augment effective anti-tumor immunity. This chapter discusses the signatures associated with immune dysfunction vs. immune-mediated rejection in cancer patients, and highlights the applications of such signatures in cancer diagnostic testing and as therapeutic opportunities. [ABSTRACT FROM AUTHOR]