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

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

Research output: Contribution to journalArticle

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

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Immunity
Head and Neck Neoplasms
Neoplasms
Phosphodiesterase 5 Inhibitors
Type 5 Cyclic Nucleotide Phosphodiesterases
Immune Evasion
Phase II Clinical Trials
Delayed Hypersensitivity
Tadalafil
Carcinoma, squamous cell of head and neck
Research Design
Cell Count
Placebos
T-Lymphocytes
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. / Califano, Joseph A.; Khan, Zubair; Noonan, Kimberly; Rudraraju, Lakshmi; Zhang, Zhe; Wang, Hao; Goodman, Steven; Gourin, Christine; Ha, Patrick K.; Fakhry, Carole; Saunders, John; Levine, Marshall; Tang, Mei; Neuner, Geoffrey; Richmon, Jeremy D.; Blanco, Ray Gervacio F.; Agrawal, Nishant; Koch, Wayne Martin; Marur, Shanthi; Weed, Donald T.; Serafini, Paolo; Borrello, Ivan M.

In: Clinical Cancer Research, Vol. 21, No. 1, 01.01.2015, p. 30-38.

Research output: Contribution to journalArticle

Califano, JA, Khan, Z, Noonan, K, Rudraraju, L, Zhang, Z, Wang, H, Goodman, S, Gourin, C, Ha, PK, Fakhry, C, Saunders, J, Levine, M, Tang, M, Neuner, G, Richmon, JD, Blanco, RGF, Agrawal, N, Koch, WM, Marur, S, Weed, DT, Serafini, P & Borrello, IM 2015, 'Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma', Clinical Cancer Research, vol. 21, no. 1, pp. 30-38. https://doi.org/10.1158/1078-0432.CCR-14-1716
Califano, Joseph A. ; Khan, Zubair ; Noonan, Kimberly ; Rudraraju, Lakshmi ; Zhang, Zhe ; Wang, Hao ; Goodman, Steven ; Gourin, Christine ; Ha, Patrick K. ; Fakhry, Carole ; Saunders, John ; Levine, Marshall ; Tang, Mei ; Neuner, Geoffrey ; Richmon, Jeremy D. ; Blanco, Ray Gervacio F. ; Agrawal, Nishant ; Koch, Wayne Martin ; Marur, Shanthi ; Weed, Donald T. ; Serafini, Paolo ; Borrello, Ivan M. / Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 1. pp. 30-38.
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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.",
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T1 - Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma

AU - Califano, Joseph A.

AU - Khan, Zubair

AU - Noonan, Kimberly

AU - Rudraraju, Lakshmi

AU - Zhang, Zhe

AU - Wang, Hao

AU - Goodman, Steven

AU - Gourin, Christine

AU - Ha, Patrick K.

AU - Fakhry, Carole

AU - Saunders, John

AU - Levine, Marshall

AU - Tang, Mei

AU - Neuner, Geoffrey

AU - Richmon, Jeremy D.

AU - Blanco, Ray Gervacio F.

AU - Agrawal, Nishant

AU - Koch, Wayne Martin

AU - Marur, Shanthi

AU - Weed, Donald T.

AU - Serafini, Paolo

AU - Borrello, Ivan M

PY - 2015/1/1

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N2 - 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.

AB - 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.

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