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

Joseph A. Califano, Zubair Khan, Kimberly A. Noonan, Lakshmi Rudraraju, Zhe Zhang, Hao Wang, Steven Goodman, Christine G. Gourin, Patrick K. Ha, Carole Fakhry, John Saunders, Marshall Levine, Mei Tang, Geoffrey Neuner, Jeremy D. Richmon, Ray Blanco, Nishant Agrawal, Wayne M. Koch, Shanthi Marur, Donald T. WeedPaolo Serafini, Ivan Borrello

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Purpose: To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells (MDSC). Experimental Design: We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma (HNSCC). Results: Tadalafil augmented immune response, increasing ex vivo T-cell expansion to a mean 2.4-fold increase compared with 1.1-fold in control patients (P = 0.01), reducing peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change in control patients (P = 0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P = 0.002). Tumor-specific immunity in response to HNSCC tumor lysate was augmented in tadalafil-treated patients (P = 0.04). Conclusions: These findings demonstrate that tadalafil augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application.

Original languageEnglish (US)
Pages (from-to)30-38
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma'. Together they form a unique fingerprint.

  • Cite this

    Califano, J. A., Khan, Z., Noonan, K. A., Rudraraju, L., Zhang, Z., Wang, H., Goodman, S., Gourin, C. G., Ha, P. K., Fakhry, C., Saunders, J., Levine, M., Tang, M., Neuner, G., Richmon, J. D., Blanco, R., Agrawal, N., Koch, W. M., Marur, S., ... Borrello, I. (2015). Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. Clinical Cancer Research, 21(1), 30-38. https://doi.org/10.1158/1078-0432.CCR-14-1716