ArticleFrontiers in oncology2021
IL-21 Is an Accomplice of PD-L1 in the Induction of PD-1-Dependent Treg Generation in Head and Neck Cancer.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 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
- Regulation of antiviral immunity by PD-1 during respiratory syncitial virus infection and upon vaccination.iScience · 2026Article
- Inflammatory response signature score model for predicting immunotherapy response and pan-cancer prognosis.Computational and structural biotechnology journal · 2024Article
- Extracellular vesicles remodel tumor environment for cancer immunotherapy.Molecular cancer · 2023Review
- Implications of IL-21 in solid tumor therapy.Medical oncology (Northwood, London, England) · 2023Review
- Clinical significance and changes to the immune microenvironment of colorectal cancer patients with liver metastasis.Journal of gastrointestinal oncology · 2023Article
- The application of Interleukin-2 family cytokines in tumor immunotherapy research.Frontiers in immunology · 2023Review
- Checkpoint inhibitor/interleukin-based combination therapy of cancer.Cancer medicine · 2022Review
- Roles for macrophage-polarizing interleukins in cancer immunity and immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T cells (Tregs) are immunosuppressive cells involved in antitumor immunity. However, the regulation of Treg generation by inflammation in the tumor microenvironment has not been carefully investigated. Here, we demonstrated that IL-21-polarized inflammation was enriched in the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) and that IL-21 could promote PD-L1-induced Treg generation in a PD-1-dependent manner. Moreover, generated Tregs showed a greater ability to suppress the proliferation of tumor-associated antigen (TAA)-specific T cells than naturally occurring Tregs. Importantly, an anti-PD-1 antibody could inhibit only Treg expansion induced by clinical tumor explants with high expression of IL-21/PD-L1. In addition, neutralizing IL-21 could enhance the anti-PD-1 antibody-mediated inhibitory effect on Treg expansion. Furthermore, simultaneous high expression of IL-21 and PD-L1 was associated with more Treg infiltrates and predicted reduced overall and disease-free survival in patients with HNSCC. These findings indicate that IL-21 in the tumor microenvironment may promote PD-L1-induced, Treg-mediated immune escape in a PD-1-dependent manner and that an IL-21 neutralization strategy may enhance PD-1 blockade-based antitumor immunotherapy by targeting Treg-mediated immune evasion in patients with high expression of IL-21 and PD-L1.
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