ArticleJCO precision oncology2025
Pan-Cancer Landscape of B- and T-Lymphocyte Attenuator: Implications for Potential Immunotherapy Combinations.
Article in JCO precision oncology, 2025. 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.
- A Tumor-Boundary Niche Enriched for PD-1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of BTLA in ovarian cancer and its clinical prognostic significance based on multi-omics analysis.Journal of ovarian research · 2026Article
- BTLA and PD-1 combined with radiotherapy for enhancing antitumor immune response in lung cancer via the regulation of memory B cells to promote T-cell infiltration.Translational lung cancer research · 2026Article
- Triple-Negative Breast Cancer: Molecular Subtypes; Immune Escape; Limitations of Current Immunotherapy; and the BTLA/HVEM/CD160 Axis as an Emerging Target.Current issues in molecular biology · 2026Review
- The Multifaceted Roles of STAT6: Implications for Precision Immunotherapeutics.ImmunoTargets and therapy · 2026Review
- BTLA: An Emerging Immune Checkpoint Target in Cancer Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- CD40 transcriptomic expression patterns across malignancies: implications for clinical trials of CD40 agonists.Cancer immunology, immunotherapy : CII · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
purposeCotargetable immune pathways for available immune checkpoint inhibitors (ICIs) may mediate response and mitigate resistance. Immune profiling may provide insights into potential immunotherapy combinations and guide ongoing clinical trials. This study investigated the transcriptomic expression and clinical implications of B- and T-lymphocyte attenuator (BTLA), a promising immune target.
methodsAltogether, 514 advanced/metastatic samples (pan-solid cancers) were analyzed using RNA sequencing. Transcriptomic expression was normalized to a reference population of 735 tumors and expressed as percentiles. BTLA, BTLA-related markers (herpes virus entry mediator [HVEM], CD160, LIGHT), and currently targetable immune pathway checkpoints (PD-1, PD-L1, PD-L2, cytotoxic T-cell lymphocyte-4 [CTLA-4], lymphocyte-activation gene 3) as well as clinical outcomes were evaluated.
resultsHigh BTLA RNA expression (≥75th percentile) was observed in 19% of tumors (96 of 514). Approximately half of these patients (44 of 96) exhibited higher coexpression (RNA) of targetable checkpoints (cluster analysis). High BTLA expression was independently associated with elevated PD-1, CTLA-4, HVEM, and CD160 RNA levels and with a breast cancer diagnosis. Outcome analysis (Kaplan-Meier) indicated that high BTLA expression correlated with significantly longer survival among ICI recipients in univariable analysis, with a trend in multivariable Cox regression (adjusted hazard ratio, 0.43 [95% CI, 0.17 to 1.08],
conclusionHigh BTLA transcript expression correlates with high transcript levels of PD-1 and CTLA-4 and with high levels of its ligand HVEM. These findings might support combining anti-PD-1 or anti-CTLA-4 therapy with anti-BTLA. BTLA expression varied across cancers and showed diverse coexpression patterns with other immune markers, suggesting that individual immunomic analysis is needed as part of a precision immunotherapy approach to understanding response and resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.