Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2015
Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00843635 (Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil), which is not on this map. Cited by 172 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pilot Study of Phosphodiesterase-5 Inhibitor Tadalafil (Cialis) as an Immunomodulator in Patients With Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
Who cites it
172 citing papers in PubMed, 2 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Trial
- Phase I/II Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Immune microenvironment modulation unmasks therapeutic benefit of radiotherapy and checkpoint inhibition.Journal for immunotherapy of cancer · 2019Trial
- PDE5A Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking through a Noncanonical cGMP-Dependent Pathway.Cancer research · 2026Article
- Assessing the therapeutic potential of PDE-5 inhibitors in adults: Insights from a multi-omics study.Physiological reports · 2026Article
- Myeloid-Derived Suppressor Cells in Cancer: Metabolic Reprogramming, Immune Crosstalk, and Therapeutic Targeting.Cancers · 2026Review
- Therapeutic repurposing of old drugs to modulate the tumor immune microenvironment and enhance immunotherapy efficacy.Journal of pharmaceutical analysis · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Characterizing the Head and Neck Cancer Microenvironment: Implications for Immunotherapy and Prognosis.Advances in experimental medicine and biology · 2026Review
- Beyond survival: psychoneuroimmunology-driven cancer psychological rehabilitation-a paradigm shift from symptom management to biobehavioral remodeling.Frontiers in oncology · 2026Review
- The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response.Frontiers in immunology · 2026Review
- Understanding the Tumor Microenvironment and Therapy Resistance in Head and Neck Squamous Cell Carcinoma.Cells · 2025Review
- Restoring dendritic cell interstitial motility via PDE5 inhibition for sustained antitumor immunity.Journal of the National Cancer Center · 2025Article
- Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer.Breast cancer research : BCR · 2025Article
- Article
- Genetically proxied inhibition of Phosphodiesterase-5 and cancer risks: A drug-target Mendelian randomization analysis.Scientific reports · 2025Article
- Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeMyeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) play a key role in the progression of head and neck squamous cell carcinoma (HNSCC). On the basis of our preclinical data demonstrating that phosphodiesterase-5 (PDE5) inhibition can modulate these cell populations, we evaluated whether the PDE5 inhibitor tadalafil can revert tumor-induced immunosuppression and promote tumor immunity in patients with HNSCC. EXPERIMENTAL
designFirst, we functionally and phenotypically characterized MDSCs in HNSCCs and determined, retrospectively, whether their presence at the tumor site correlates with recurrence. Then, we performed a prospective single-center, double-blinded, randomized, three-arm study in which patients with HNSCC undergoing definitive surgical resection of oral and oropharyngeal tumors were treated with tadalafil 10 mg/day, 20 mg/day, or placebo for at least 20 days preoperatively. Blood and tumor MDSC and Treg presence and CD8(+) T-cell reactivity to tumor antigens were evaluated before and after treatment.
resultsMDSCs were characterized in HNSCC and their intratumoral presence significantly correlates with recurrence. Tadalafil treatment was well tolerated and significantly reduced both MDSCs and Treg concentrations in the blood and in the tumor (P < 0.05). In addition, the concentration of blood CD8(+) T cells reactive to autologous tumor antigens significantly increased after treatment (P < 0.05). Tadalafil immunomodulatory activity was maximized at an intermediate dose but not at higher doses. Mechanistic analysis suggests a possible off-target effect on PDE11 at high dosages that, by increasing intracellular cAMP, may negatively affect antitumor immunity.
conclusionsTadalafil seems to beneficially modulate the tumor micro- and macro-environment in patients with HNSCC by lowering MDSCs and Tregs and increasing tumor-specific CD8(+) T cells in a dose-dependent fashion.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.