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PDE5 inhibition abrogates MDSC suppressive activity
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How Effective Are the Implants?
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PDE5 blockade not only increases intratumoral CD8+ infiltration and activation but also enhances their tumoricidal activity (Fig. 2). The ability to favorably alter the intratumoral microenvironment, thereby permitting tumor-specific T cells to directly interact with their targets, is critical for maximal antitumor immunity. Effective immunotherapy requires tumor-specific CTLs to infiltrate the tumor and kill their target in situ. Although no clinical advantage was derived by the presence of tumor-specific CTLs in the peripheral blood in melanoma patients (40), their frequency in the tumor correlated with a favorable prognosis (41). These clinical observations seem to be confirmed in our model where sildenafil treatment (a) increased the CD8+ T cell tumor infiltration (Fig. 4 B) and (b) increased the percentage of activated T cells (Fig. 4, C and D). Moreover, the number of tumor-infiltrating T cells directly correlated with a measurable antitumor effect (Fig. 3).
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