ArticleFrontiers in immunology2022
CD137 Agonists Targeting CD137-Mediated Negative Regulation Show Enhanced Antitumor Efficacy in Lung Cancer.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- IFN-γ PET imaging stratifies and predicts response to CD137 agonism in a syngeneic colorectal tumor model.Journal for immunotherapy of cancer · 2026Article
- Development and validation of highly sensitive ligand binding assay to measure soluble DLL3 concentration in human serum.Bioanalysis · 2025Article
- The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer.Cell death & disease · 2025Review
- One-carbon metabolism is distinct metabolic signature for proliferative intermediate exhausted T cells of ICB-resistant cancer patients.Cell death discovery · 2025Article
- CD137 in tuberculosis: a scoping review of an emerging immune checkpoint at the crossroads of diagnosis, prognosis, and therapy.Frontiers in immunology · 2025Article
- Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer.ERJ open research · 2024Article
- PCSK9 regulates the efficacy of immune checkpoint therapy in lung cancer.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Negative immune regulation plays a notable role in tumor immunity. This study aimed to confirm that CD137 mediates negative immunoregulation as well as agonist activity in tumor immunity. Soluble CD137 (sCD137), a prominent splice variant of membrane-bound CD137 (mCD137), was identified, and its concentration in the blood of lung cancer patients was increased. The baseline concentration of sCD137 in the blood was negatively correlated with the efficacy of neoadjuvant immunochemotherapy in a pilot study. The percentage of CD137+ regulatory T cells (Tregs) in the blood of lung cancer patients was also increased, and further enriched at the tumor site; Foxp3, CTLA-4, IL-10, IL-35-Ebi3, sCD137 and costimulatory molecules expression were also higher, indicating increased immunosuppressive activity. A high percentage of CD137+ Tregs in the tumor was associated with worse OS outcomes among patients with high CD137+CD8+ T cell infiltration levels. Notably, targeting CD137+ Tregs using an engineered CD137 agonist with wild-type mouse IgG2a Fc clearly decreased the total Treg numbers and eliminated the tumor in the CT26 model and prolonged the survival rate of a Lewis lung carcinoma (LLC) model. These results indicated it may be possible to empower CD137 agonist with ability to abolish CD137-mediated negative regulation to enhance its antitumor efficacy.
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