ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020
Looking past PD-L1: expression of immune checkpoint TIM-3 and its ligand galectin-9 in cervical and vulvar squamous neoplasia.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Positivity Rate of PD-L1 Expression and Its Clinical Significance in Vulvar Cancer: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Prognostic Impact and Clinicopathological Significance of TIM-3 and LAG-3 Expressions in Laryngeal Squamous Cell Carcinoma.Laryngoscope investigative otolaryngology · 2026Article
- Role of hypoxia-inducible factor - 1 alpha on the progression of cervical intraepithelial neoplasia and cervical cancer: a narrative review.Frontiers in oncology · 2026Review
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- Tumor-Infiltrating Lymphocytes in Breast and Female Genital Tract Cancers: Overlooked Potential and Unexplored Frontiers.Cancer medicine · 2025Review
- Cell-associated galectin 9 interacts with cytotoxic T cells confers resistance to tumor killing in nasopharyngeal carcinoma through autophagy activation.Cellular & molecular immunology · 2025Article
- Prognostic assessment of cervical cancer based on biomarkers: the interaction of ERRα and immune microenvironment.Virology journal · 2025Article
- Aberrant expression of PYGB as a potential therapeutic target and its associations with immune cell infiltration in lung cancer.Frontiers in immunology · 2025Article
- MFSD12 promotes proliferation, metastasis and invasion of hepatocellular carcinoma cells and its potential correlation with HAVCR2/LGALS9 immune checkpoint axis.Frontiers in immunology · 2025Article
- CHMP4A in hepatocellular carcinoma: exploring its role in tumor progression, immune modulation, and potential link to TIM3 checkpoint.Frontiers in immunology · 2025Article
- Unravelling the Reasons Behind Limited Response to Anti-PD Therapy in ATC: A Comprehensive Evaluation of Tumor-Infiltrating Immune Cells and Checkpoints.Endocrine pathology · 2024Article
- The immunosuppressive landscape in tumor microenvironment.Immunologic research · 2024Review
- Expression of B7-H3 and TIM-3 in gastric-type endocervical adenocarcinoma: prevalence, association with PD-L1 expression, and prognostic significance.The journal of pathology. Clinical research · 2024Article
- Case report: Giant lymph node metastases: a new opportunity for cancer radioimmunotherapy?Frontiers in immunology · 2024Article
- Charting new frontiers: Co-inhibitory immune checkpoint proteins in therapeutics, biomarkers, and drug delivery systems in cancer care.Translational oncology · 2023Article
- Galectin-9 in cancer therapy: from immune checkpoint ligand to promising therapeutic target.Frontiers in cell and developmental biology · 2023Review
- The Features of Checkpoint Receptor-Ligand Interaction in Cancer and the Therapeutic Effectiveness of Their Inhibition.Biomedicines · 2022Review
- Targeting immune checkpoints in gynecologic cancer: updates & perspectives for pathologists.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Review
- A Novel Prognostic Risk Model for Cervical Cancer Based on Immune Checkpoint HLA-G-Driven Differentially Expressed Genes.Frontiers in immunology · 2022Article
- Emerging Therapeutic Strategies of Different Immunotherapy Approaches Combined with PD-1/PD-L1 Blockade in Cervical Cancer.Drug design, development and therapy · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapies targeting the PD-1/PD-L1 pathway have shown some success in cervical and vulvar squamous cell carcinomas, but little is known about the potential vulnerability of these tumors to other checkpoint inhibitors. TIM-3 is a checkpoint molecule that exerts immunosuppressive function via its interaction with Gal-9. TIM-3 and Gal-9 have been identified on a variety of malignancies but have not been studied in cervical and vulvar cancers, nor has their relationship to PD-L1 been established. Sixty-three cervical and vulvar invasive (n = 34) and intraepithelial lesions (n = 29) were assessed for TIM-3, Gal-9, and PD-L1 in tumor/lesional cells and associated immune cells. Tumoral TIM-3 expression was identified in 85% of squamous cell carcinomas but only 21% of intraepithelial lesions (p < 0.0001). When immune cells were also accounted for, 97% of invasive and 41% of intraepithelial lesions had a TIM-3 combined positive score (CPS) ≥ 1 (p < 0.0001). Tumoral membranous expression of Gal-9 was seen in 82% of squamous cell carcinomas and 31% of intraepithelial lesions (p = 0.0001); nearly all cases had Gal-9-positive immune cells. Tumoral PD-L1 was seen in 71% of squamous cell carcinomas and 10% of intraepithelial lesions (p < 0.0001), while the PD-L1 CPS was ≥1 in 82 and 21%, respectively (p < 0.0001). There were no significant differences in TIM-3, GAL-9, or PD-L1 expression in cervical vs. vulvar neoplasms, nor was HPV status significantly associated with any of the three markers. Dual TIM-3/Gal-9 expression was present in the majority (86%) of PD-L1-positive cases including 100% of PD-L1-positive squamous cell carcinomas, suggesting a possible role for TIM-3 checkpoint inhibition in concert with anti-PD-1/PD-L1.
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