ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Immune suppression in premalignant respiratory papillomas: enriched functional CD4+Foxp3+ regulatory T cells and PD-1/PD-L1/L2 expression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Prognostic value of PD-1, PD-L1 and PD-L2 deserves attention in head and neck cancer.Frontiers in immunology · 2022Pooled it
- Clinicopathological and prognostic significance of PD-L1 expression in sarcoma: A systematic review and meta-analysis.Medicine · 2018Pooled it
- DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety, and immunogenicity of INO-3107.Nature communications · 2025Trial
- Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Trial
- Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.Journal for immunotherapy of cancer · 2021Trial
- Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study.Arthritis research & therapy · 2021Trial
- Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis.Journal for immunotherapy of cancer · 2019Trial
- T(H)2-like chemokine patterns correlate with disease severity in patients with recurrent respiratory papillomatosis.Molecular medicine (Cambridge, Mass.) · 2012Trial
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Article
- Comparison of circulating immune signatures across different consensus molecular subtypes (CMS) and between left- and right-sided lesions in stage II colorectal cancer using single-cell mass cytometry.Journal of translational medicine · 2025Article
- Characterization of HPV6/11-reactive T-cell subsets in papillomas of patients with juvenile-onset recurrent respiratory papillomatosis and identification of HPV11 E7-specific candidate TCR clonotypes.Journal of virology · 2024Article
- Quantification and Functional Studies of Neutrophilic Cells Identifies Distinct Papilloma Phenotypes.The Laryngoscope · 2024Article
- Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.The Laryngoscope · 2024Article
- Impact of the response to platinum-based chemotherapy on the second-line immune checkpoint inhibitor monotherapy in non-small cell lung cancer with PD-L1 expression ≤49%: a multicenter retrospective study.Frontiers in oncology · 2024Article
- Molecular Mechanisms of Carcinogenesis in Pediatric Airways Tumors.International journal of molecular sciences · 2023Review
- Prevalence of viral DNA in high-grade serous epithelial ovarian cancer and correlation with clinical outcomes.PloS one · 2023Article
- TP53TG1/STAT axis is involved in the development of colon cancer through affecting PD-L1 expression and immune escape mechanism of tumor cells.American journal of cancer research · 2023Article
- Restricted Recruitment of NK Cells with Impaired Function Is Caused by HPV-Driven Immunosuppressive Microenvironment of Papillomas in Aggressive Juvenile-Onset Recurrent Respiratory Papillomatosis Patients.Journal of virology · 2022Article
- Tumor-associated antigen PRAME exhibits dualistic functions that are targetable in diffuse large B cell lymphoma.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeRespiratory papillomas, caused by human papillomaviruses types 6 and 11 (HPV6/11), are premalignant lesions with potential for malignant conversion. The cytokine and chemokine micromilieu of papillomas is T(H)2-like with a marked absence of IFN-γ expression. To illuminate why patients with recurrent respiratory papillomatosis (RRP) fail to effectively control their disease, we further investigated the suppressive cellular microenvironment in papillomas. EXPERIMENTAL
designCD4(+)CD25(+)CD127(low/-)Foxp3(+) regulatory T cells (Treg) and CD4(+)CD25(-)CD127(low/-)Foxp3(-) T cells within papillomas were characterized and isolated. Their suppressor function was measured by inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Expression of PD-1, CD69, and Helios was identified on these T cells. PD-L1, PD-L2, CCL17, and CCL22 mRNA was also identified in papillomas by quantitative PCR.
resultsFunctional Tregs were markedly enriched in papillomas and strongly inhibited anti-CD3 and anti-CD28 antibody activated PBMC proliferation. The natural Treg marker Helios was reduced on Tregs from papillomas, indicating that the majority of Tregs in papillomas are adaptive. The majority of the papilloma-derived CD4(+) T cells expressed the CD4(+)CD25(-)CD127(low/-)Foxp3(-)PD1(+)CD69(+) phenotype and failed to suppress PBMC proliferation, suggesting that they are chronically activated and exhausted. The Treg-attracting chemokine CCL22 was equally expressed by all laryngeal tissues examined. However, CCL17 was robustly expressed by papillomas compared with unaffected laryngeal tissues from RRP patients and individuals without RRP. PD-L1 was elevated in papillomas compared with control laryngeal tissues.
conclusionsPapilloma CD4(+) T cells are enriched with functional Tregs, and the adaptive Helios(-) Treg fraction was increased within the T(H)2-like papilloma micromilieu. CD4(+)CD25(-)CD127(low/-)Foxp3(-) T-cells failed to suppress PBMC proliferation and may be exhausted. The PD-1/PDL-1 pathway may represent an additional immunosuppressive mechanism that contributes to defective HPV6/11 clearance in RRP.
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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.