ArticleCancer immunology, immunotherapy : CII2017
CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases.
Article in Cancer immunology, immunotherapy : CII, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- CTLA-4 polymorphisms and predisposition to digestive system malignancies: a meta-analysis of 31 published studies.World journal of surgical oncology · 2020Pooled it
- Cellular immunotherapy for lung cancer: current clinical evidence, translational challenges, and future perspectives: a narrative review.Translational cancer research · 2026Article
- Interrelationships Between PD-L1, CTLA-4, IL-10 and IL-18 Expression in Oral Squamous Cell Carcinoma.Current issues in molecular biology · 2026Article
- Obstructive sleep apnea as a modifier of endocrine toxicities associated with immune checkpoint inhibitors in lung cancer.Frontiers in immunology · 2026Review
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- Dendritic Cells of Leukemic Origin (DCCancers · 2025Article
- A molecular and immunohistochemical study of 37 cases of ovarian Sertoli-Leydig cell tumor.Virchows Archiv : an international journal of pathology · 2025Article
- Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue.Pathogens (Basel, Switzerland) · 2025Article
- The Current State of Tumor Microenvironment-Specific Therapies for Non-Small Cell Lung Cancer.Cancers · 2025Review
- Article
- Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.The Journal of cell biology · 2025Article
- Article
- An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.Virchows Archiv : an international journal of pathology · 2024Article
- Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma.The Journal of clinical endocrinology and metabolism · 2024Article
- Identification of Two Distinct Immune Subtypes in Hepatitis B Virus (HBV)-Associated Hepatocellular Carcinoma (HCC).Cancers · 2024Article
- NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy.Frontiers in immunology · 2024Review
- Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.bioRxiv : the preprint server for biology · 2024Article
- Recent advances in non-small cell lung cancer targeted therapy; an update review.Cancer cell international · 2023Review
- CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma.Clinical epigenetics · 2023Article
- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) as an undetermined tool in tumor cells.Human cell · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes. CTLA-4 expression in neither tumor epithelial cells (T-CTLA-4) nor stromal cells (S-CTLA-4) of primary tumors was significantly associated with disease-specific survival (DSS) in all patients. However, high S-CTLA-4 expression independently predicted significantly improved DSS in the squamous cell carcinoma subgroup (HR 0.62, 95% CI 0.41-0.93, P = 0.021). In contrast, there was an independent negative prognostic impact of T-CTLA-4 expression in metastatic lymph nodes (HR 1.65, 95% CI 1.03-2.65, P = 0.039). Our results indicate that the expression of CTLA-4 has diverging prognostic impacts in metastatic NSCLC lymph nodes versus primary tumors. The presented results highlight important differences in the tumor microenvironments of primary and metastatic NSCLC tissues, and have potential to guide treatment and clinical sampling strategies.
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