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 Weed; Paolo Serafini; Ivan Borrello

doi:10.1158/1078-0432.CCR-14-1716

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

Journal article

Open access

Peer reviewed

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, …

Clinical cancer research, Vol.21(1), pp.30-38

2015-01-01

DOI: https://doi.org/10.1158/1078-0432.CCR-14-1716

PMCID: PMC4329916

PMID: 25564570

Abstract

Carcinoma, Squamous Cell - enzymology

Humans

Middle Aged

Head and Neck Neoplasms - drug therapy

Phosphodiesterase 5 Inhibitors - administration & dosage

Male

Carbolines - administration & dosage

Carcinoma, Squamous Cell - immunology

Tadalafil

Head and Neck Neoplasms - immunology

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Squamous Cell - drug therapy

Immunity, Cellular - drug effects

T-Lymphocytes - drug effects

Aged, 80 and over

Cyclic Nucleotide Phosphodiesterases, Type 5 - genetics

Adult

Female

T-Lymphocytes - immunology

Aged

Cyclic Nucleotide Phosphodiesterases, Type 5 - immunology

Head and Neck Neoplasms - enzymology

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). 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). 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). 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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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.214 PD-1
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma
Creators: Joseph A Califano - Department 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
Zubair Khan - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
Kimberly A Noonan - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
Lakshmi Rudraraju - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
Zhe Zhang - Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
Hao Wang - Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
Steven Goodman - Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
Christine G Gourin - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
Patrick K Ha - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland. Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland
Carole Fakhry - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland. Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland
John Saunders - Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland
Marshall Levine - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. Oncology Department, Greater Baltimore Medical Center, Baltimore, Maryland
Mei Tang - Oncology Department, Greater Baltimore Medical Center, Baltimore, Maryland
Geoffrey Neuner - Oncology Department, Greater Baltimore Medical Center, Baltimore, Maryland
Jeremy D Richmon - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
Ray Blanco - Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland
Nishant Agrawal - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
Wayne M Koch - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
Shanthi Marur - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
Donald T Weed - Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida
Paolo Serafini - Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida
Ivan Borrello - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. jcalifa@jhmi.edu iborrell@jhmi.edu
Publication Details: Clinical cancer research, Vol.21(1), pp.30-38
Publisher: United States
Grant note: 1R21CA135635 / NCI NIH HHS P50 DE019032 / NIDCR NIH HHS P50 CA096784 / NCI NIH HHS R21 CA135635 / NCI NIH HHS P50 CA19032 / NCI NIH HHS
Academic Unit: Miller School of Medicine; Interdisciplinary Stem Cell Institute; Microbiology and Immunology Research; UMMG Department of Otolaryngology
Language: English
Resource Type: Journal article
PMID: 25564570
PMCID: PMC4329916
Record Identifier: 991031561085402976