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BALB/c mice were injected with PBS (naive), vaccinated with -irradiated CT26WT or C26GM, or challenged with CT26WT or C26GM tumors on day 0. On day 12 (CT26WT) or day 5 (C26GM), all mice received carboxyfluorescein diacetate succinimidyl ester (CFSE)–labeled splenocytes pulsed with the MHC class I–restricted AH-1 peptide (CFSEhigh), admixed with CFSE-labeled splenocytes pulsed with the irrelevant hemagglutinin (HA)-peptide (CFSElow). In vivo T cell cytotoxicity was determined 40 h later (Fig. 2). These time points were chosen based on the kinetics of tumor outgrowth observed in Fig. 1 A and Fig. 1 B, respectively, when tumor size significantly differed between untreated and sildenafil-treated mice. As expected, an endogenous AH1-specific immune response was observed in the vaccinated mice as compared with their tumor-bearing counterparts. PDE5 inhibition in the vaccine-primed mice failed to augment antigen-specific CD8 responsiveness compared with no treatment. In contrast, tumor-bearing mice treated with sildenafil early after tumor challenge generated antigen-specific immunity that was significantly greater then that observed in their untreated counterparts and similar, or even superior, to that induced by vaccination. Collectively, this is the first indication that PDE5 inhibitors can modulate antitumor immunity. Because the sildenafil-mediated antitumor immune response does not completely eradicate tumors, tumor escape mechanisms may be associated with their outgrowth. To test this hypothesis, the parental CT26WT cell line, as well as the CT26 tumor removed on day 24 from sildenafil-treated mice (either AH-1 pulsed or unpulsed), and BALB/c splenocytes were incubated with either AH-1 peptide-primed (Fig. S1 C) or tumor-primed (Fig. S1 D) effector T cells. Although effector T cells recognized the parental CT26WT line and released IFN- in the assay, they failed to recognize the sildenafil-derived tumor. Its recognition, however, was restored by loading the sildenafil-derived tumor with the AH-1 peptide. (Fig. S1, C and D). These results suggest that the immune response in sildenafil-treated mice does not result in complete tumor eradication but rather in the selection of antigen-escape variants. If the man's life expectancy is low due to old age or other factors, surgery or radiation for prostate cancer might actually do more harm than good, some doctors feel. What should I or my partner do if a severe reaction occurs? Depression Psychological illnesses Lacks formal FDA† approval (except for prostaglandin [ie, Caverject, Edex])

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