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We next sought to determine whether we could restore T cell proliferation of PBMCs isolated from head and neck and MM patients stimulated with anti-CD3/CD28 antibody-coated beads in the presence or absence of sildenafil. The expansion of CD4+ and CD8+ T cells obtained from MM or head and neck patients was significantly less than that observed using healthy donors (Fig. 8 B). In contrast, in the presence of sildenafil, PBMCs from MM and head and neck patients expanded similarly to sildenafil-treated PBMCs from healthy donors (Fig.8 B). Interestingly, qualitative differences in T cell expansion emerged between the two malignancies. In head and neck patients, CD8+ T cell proliferation is restored with PDE5 inhibition while CD4+ lymphocyte expansion in the same condition is only partially augmented. In contrast, CD4+ T cell proliferation is restored and minimal effects are seen on CD8+ lymphocyte expansion with PDE5 blockade in myeloma (Fig. 8 B). 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