BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination
| Autor: | Daniel E. Speiser, Pedro Romero, Laurent Derré, Camilla Jandus, Olivier Michielin, Daniel Olive, Sonia Pastor, Jean-Paul Rivals, Donata Rimoldi |
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| Rok vydání: | 2010 |
| Předmět: |
T-Lymphocytes
T cell medicine.medical_treatment BTLA Biology GPI-Linked Proteins Animals Antigens CD/physiology Antigens Neoplasm/immunology Apoptosis Regulatory Proteins/physiology CD8-Positive T-Lymphocytes/immunology COS Cells Cell Line Tumor Cercopithecus aethiops Humans Interferon-gamma/biosynthesis Lymphocyte Activation MART-1 Antigen Melanoma/immunology Melanoma/therapy Neoplasm Proteins/immunology Oligodeoxyribonucleotides/pharmacology Receptors Immunologic/physiology Receptors Tumor Necrosis Factor Member 14/physiology Vaccination Immune system Antigen Antigens CD Antigens Neoplasm Neoplasms medicine Cytotoxic T cell CTLA-4 Antigen Receptors Immunologic General Medicine T lymphocyte Immunotherapy Neoplasm Proteins medicine.anatomical_structure Oligodeoxyribonucleotides Immunology Cancer research CD8 Research Article |
| Zdroj: | Journal of Clinical Investigation, vol. 120, no. 1, pp. 157-167 Derré, Laurent; Rivals, Jean-Paul; Jandus, Camilla; Pastor, Sonia; Rimoldi, Donata; Romero, Pedro; Michielin, Olivier; Olive, Daniel; Speiser, Daniel E (2010). BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. Journal of clinical investigation, 120(1), pp. 157-67. Ann Arbor, Mich.: American Society for Clinical Investigation 10.1172/JCI40070 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci40070 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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