ArticleOncoimmunology
OX40 expression in hepatocellular carcinoma is associated with a distinct immune microenvironment, specific mutation signature, and poor prognosis.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma.BMC cancer · 2022Pooled it
- Pooled it
- Breakthroughs in HBV-related HCC Therapy: The Unmatched Potential of Immune Checkpoint Inhibitors.Current treatment options in oncology · 2026Review
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Expression and prognostic importance of lymphocyte activation gene 3 and CD73 in advanced or metastatic hepatocellular carcinoma.The Journal of international medical research · 2026Article
- OX40 transcriptomic expression and its association with immune checkpoints and clinical outcomes.Therapeutic advances in medical oncology · 2026Article
- The role of tumor necrosis factor receptor superfamily in cancer: insights into oncogenesis, progression, and therapeutic strategies.NPJ precision oncology · 2025Review
- Emerging Immunotherapy Targets in Early Drug Development.International journal of molecular sciences · 2025Review
- Spatial heterogeneity of the hepatocellular carcinoma microenvironment determines the efficacy of immunotherapy.Discover oncology · 2025Review
- ALG3 as a prognostic biomarker and mediator of PD-1 blockade resistance in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- OX40/OX40L: a new target for tumor immunotherapy and its clinical research progress.Frontiers in oncology · 2025Review
- OX40/OX40 ligand and its role in precision immune oncology.Cancer metastasis reviews · 2024Review
- Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer.International journal of molecular sciences · 2024Article
- Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers - how to push the gas after having released the brake.Frontiers in immunology · 2024Review
- Costimulatory Molecules OX40 and OX40L Upregulation in Oral Squamous Cell Carcinoma: A Blood-Based Study.European journal of dentistry · 2023Article
- YAP1 expression is associated with survival and immunosuppression in small cell lung cancer.Cell death & disease · 2023Article
- Lung tumor-infiltrating TScience immunology · 2023Article
- Review
- Elevated expression of TNFRSF4 impacts immune cell infiltration and gene mutation in hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2023Article
- T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosisFrontiers in immunology · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy's effect against hepatocellular carcinoma (HCC) is hampered by immunosuppressive mechanisms in the tumor microenvironment. We assessed the clinicopathologic and biologic relevance of OX40, a costimulatory molecular expressed by regulatory T cells (Tregs), in HCC. We analyzed the immunohistochemistry data of 316 patients treated at West China Hospital (WCH) and the RNA sequencing data of 370 patients in The Cancer Genome Atlas (TCGA) to determine the clinicopathologic significance of OX40 in HCC. We also assessed associations between OX40 and multiple immune-related markers. Using the TCGA data, we further characterized the transcriptome, immune cell functions, and mutation signature related to OX40. We found that OX40 expression was higher in HCC than in adjacent liver tissue. In the WCH set, 136 (43%) patients had high-OX40 expression, whereas in the TCGA set, 247 (67%) patients had high-OX40 expression as determined by the X-tile program. High-OX40 expression was associated with high serum alpha-fetoprotein level, vascular invasion, and shorter survival. The prognostic significance of OX40 was validated in additional cohorts. OX40 expression was also associated with CD8A, CD68, LAG3, TIM-3, and PD-1 expression. High-OX40 expression tumors were characterized by upregulated cytokines and exhaustion-specific markers. Analysis of the enrichment data of immune cell types indicated that OX40 expression was associated with the functions of macrophages, plasmacytoid dendritic cells, and co-inhibitory T cells. Finally, high-and low-OX40 expressions were associated with mutations in AKT/mTOR and Wnt/β-catenin signaling, respectively. These results indicate that high-OX40 expression represents the activation of multiple immunosuppressive pathways and provide a rationale for the therapeutic targeting OX40 in HCC patients.
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