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These findings could establish a new role for PDE5 inhibition as a viable and effective immunological adjunct in the treatment of various malignancies, thereby adding to the growing list of therapeutic applications of these agents. In this paper we show that PDE5 inhibition can significantly overcome the immunosuppressive mechanisms present in a tumor-bearing host to generate immune responses that are similar to (if not greater than) those observed in a non� tumor-bearing, vaccine-primed host (Fig. 2). However, although a CTL response can be elicited, PDE5 blockade is incapable of complete tumor eradication (Fig. S1). Several hypotheses may account for these findings. For example, chronic sildenafil blockade may up-regulate PDE5 expression, making it difficult to achieve complete and long-term pharmacologic inhibition (39). 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