ArticleCancer medicine2025
LAG3 as a Tumor Suppressor and Immune Regulator in Cervical Cancer: From Functional Validation to Therapeutic Strategy.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Virus infections and cancers: from mechanisms to therapeutics.Molecular biomedicine · 2026Review
- Immune remodeling during cervical cancer chemoradiotherapy: temporal biomarkers and the timing of checkpoint blockade.Frontiers in immunology · 2026Review
- LAG3 as a Tumor Suppressor and Immune Regulator in Cervical Cancer: From Functional Validation to Therapeutic Strategy.Cancer medicine · 2025Article
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8 authors.
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Abstract
backgroundCervical cancer remains a significant health burden for women worldwide, with persistent high-risk HPV infection being a major etiological factor. Despite treatment advances, prognosis for recurrent or metastatic disease remains poor. Pyroptosis, a form of programmed cell death, plays a dual role in tumor immunity, but its implications in cervical cancer are not fully elucidated. This study aims to systematically characterize pyroptosis-related genes (PRGs) in cervical cancer and explore their prognostic and therapeutic relevance.
methodsMulti-omics data from TCGA and GEO databases were integrated to analyze genetic variations, expression patterns, and prognostic significance of 52 PRGs in cervical cancer. Consensus clustering was used to identify PRG subtypes. A prognostic risk score model was constructed using LASSO-Cox regression based on differentially expressed genes (DEGs). Functional validation was performed via in vitro and in vivo experiments, including Western blot, CCK-8, colony formation, transwell assays, and a subcutaneous tumor model. Single-cell RNA sequencing data (GSE171894, GSE168652) were analyzed to explore LAG3 expression in the tumor immune microenvironment.
resultsTwo distinct PRG subtypes were identified, with subtype A showing immune activation features. A five-gene prognostic signature (GNAZ, LAG3, IL-1β, CA2, SPRR3) effectively stratified patients into high- and low-risk groups. Low LAG3 expression was associated with poor prognosis. Functional experiments demonstrated that LAG3 overexpression suppressed cervical cancer cell proliferation, migration, and tumor growth, while its knockdown promoted malignant phenotypes. Single-cell analysis revealed high LAG3 expression in Treg and CD8⁺ T cells, suggesting its role in immune regulation.
conclusionThis study establishes a novel PRG-based prognostic model and highlights LAG3 as a key tumor suppressor and immune regulator in cervical cancer. These findings provide insights into the interplay between pyroptosis and antitumor immunity, supporting LAG3 as a potential therapeutic target for cervical cancer immunotherapy.
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