ArticleThe Journal of clinical investigation2010
BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
160 citing papers in PubMed, 287 citations in OpenAlex.
- Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- The BTLA/HVEM axis as a key regulator for stratified functional cure in chronic hepatitis B.Frontiers in immunology · 2026Review
- Single cell mapping of B and T cell dynamics in breast cancer lymph node metastasis.Frontiers in bioinformatics · 2026Article
- CD160-Derived Peptide as a Bidirectional Inhibitor Toward Immune Checkpoints BTLA/HVEM and HVEM/LIGHT.Journal of medicinal chemistry · 2025Article
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- BTLA: An Emerging Immune Checkpoint Target in Cancer Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Pan-Cancer Landscape of B- and T-Lymphocyte Attenuator: Implications for Potential Immunotherapy Combinations.JCO precision oncology · 2025Article
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
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- Article
- Single-Cell RNA Profiling of Ocular Adnexal Sebaceous Carcinoma Reveals a Complex Tumor Microenvironment and Identifies New Biomarkers.American journal of ophthalmology · 2025Observational
- Integrated Analysis of Single-Cell and Bulk RNA Data Reveals Complexity and Significance of the Melanoma Interactome.Cancers · 2025Article
- Immediate variations in high-dimensional circulating immune cells following pancreatectomy.Clinical & translational immunology · 2025Article
- B and T lymphocyte attenuator (BTLA) and PD-1 pathway dual blockade promotes antitumor immune responses by reversing CD8Frontiers in immunology · 2025Article
- Perioperative the BTLA inhibitor (tifcemalimab) combined with toripalimab and chemotherapy for resectable locally advanced thoracic esophageal squamous cell carcinoma trial (BT-NICE trial): a prospective, single-arm, exploratory study.Frontiers in immunology · 2025Article
- Immunotherapy and delivery systems for melanoma.Human vaccines & immunotherapeutics · 2024Review
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- The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.Nature immunology · 2024Article
- The role of the BTLA-HVEM complex in the pathogenesis of breast cancer.Breast cancer (Tokyo, Japan) · 2024Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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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 function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.
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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 OpenQuestion graph.