Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma.
Level 2 - randomized trial
Prospective, double-blind, randomized, placebo-controlled trial
PubMed 25320361 · doi:10.1158/1078-0432.CCR-14-1711
What was done
The authors characterized myeloid-derived suppressor cells (MDSCs) in head and neck squamous cell carcinoma (HNSCC) and retrospectively analyzed their correlation with recurrence. They then conducted a prospective, single-center, double-blind, randomized, three-arm trial in patients with oral and oropharyngeal HNSCC undergoing surgical resection. Patients were treated preoperatively for at least 20 days with tadalafil 10 mg/day, tadalafil 20 mg/day, or placebo. Blood and intratumoral MDSCs and regulatory T cells (Tregs), along with CD8+ T-cell reactivity against autologous tumor antigens, were measured pre- and post-treatment.
What was found
Intratumoral MDSC presence was significantly associated with cancer recurrence in the retrospective cohort. In the randomized trial, tadalafil significantly reduced both MDSC and Treg concentrations in peripheral blood and within the tumor (P < 0.05). Circulating tumor-reactive CD8+ T-cell levels increased significantly following treatment (P < 0.05). Immunomodulatory activity peaked at the intermediate dose (10 mg/day) rather than the higher dose (20 mg/day). The abstract reports no sample sizes, baseline figures, effect sizes, or confidence intervals.
Why it matters
This study demonstrates that the phosphodiesterase-5 inhibitor tadalafil can reduce immunosuppressive cell populations and boost tumor-specific immune responses in patients with HNSCC.
Limits
The abstract omits patient sample sizes, exact numeric measurements, and confidence intervals. The trial was single-center with short-term preoperative dosing (≥20 days) and evaluated surrogate immunologic markers rather than long-term clinical survival or disease recurrence.
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