Format

Send to

Choose Destination
Clin Cancer Res. 2015 Jan 1;21(1):30-8. doi: 10.1158/1078-0432.CCR-14-1716.

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

Author information

1
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.
2
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
3
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
4
Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
5
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.
6
Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
7
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. Oncology Department, Greater Baltimore Medical Center, Baltimore, Maryland.
8
Oncology Department, Greater Baltimore Medical Center, Baltimore, Maryland.
9
Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
10
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida.
11
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. jcalifa@jhmi.edu iborrell@jhmi.edu.

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.

PMID:
25564570
PMCID:
PMC4329916
DOI:
10.1158/1078-0432.CCR-14-1716
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center