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Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma

Joseph A Califano1, Zubair Khan2, Kimberly A Noonan3

  • 1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland. jcalifa@jhmi.edu iborrell@jhmi.edu.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 8, 2015
PubMed
Abstract

Insights

Phosphodiesterase 5 (PDE5) inhibitors like tadalafil can boost immune responses in head and neck cancer patients. This drug reduced immunosuppressive cells and enhanced both general and tumor-specific immunity, showing therapeutic potential.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is characterized by immune evasion and suppressed immunity.
  • Myeloid-derived suppressor cells (MDSC) play a crucial role in tumor-induced immunosuppression.
  • Targeting immune suppressive mechanisms offers a potential therapeutic strategy for HNSCC.

Purpose of the Study:

  • To investigate the immunomodulatory effects of phosphodiesterase 5 (PDE5) inhibitors in patients with HNSCC.
  • To determine if PDE5 inhibition can reduce the number and function of MDSC.
  • To assess the impact of PDE5 inhibitors on both general and tumor-specific immune responses.

Main Methods:

  • A randomized, prospective, double-blinded, placebo-controlled phase II clinical trial was conducted.
  • Systemic administration of tadalafil (a PDE5 inhibitor) or placebo was given to HNSCC patients.
  • Immune function was assessed by measuring T-cell expansion, peripheral MDSC numbers, delayed-type hypersensitivity response, and tumor-specific immunity.

Main Results:

  • Tadalafil significantly increased ex vivo T-cell expansion compared to placebo (2.4-fold vs. 1.1-fold).
  • Tadalafil treatment led to a significant reduction in peripheral MDSC numbers (0.81-fold change vs. 1.26-fold change).
  • General immunity (delayed-type hypersensitivity) and tumor-specific immunity against HNSCC tumor lysate were augmented in the tadalafil group.

Conclusions:

  • Tadalafil effectively augments both general and tumor-specific immunity in patients with HNSCC.
  • PDE5 inhibition with tadalafil demonstrates potential therapeutic application by reversing immune suppression in head and neck cancer.
  • These findings suggest that targeting PDE5 pathways could be a viable strategy to enhance anti-tumor immunity in HNSCC.

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