論文 - 詳細
| RRC ID | 5999 |
|---|---|
| 著者 | Mumprecht S, Schürch C, Schwaller J, Solenthaler M, Ochsenbein AF. |
| タイトル | Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. |
| ジャーナル | Blood |
| Abstract |
Chronic myeloid leukemia (CML) is a malignant myeloproliferative disease with a characteristic chronic phase (cp) of several years before progression to blast crisis (bc). The immune system may contribute to disease control in CML. We analyzed leukemia-specific immune responses in cpCML and bcCML in a retroviral-induced murine CML model. In the presence of cpCML and bcCML expressing the glycoprotein of lymphocytic choriomeningitis virus as a model leukemia antigen, leukemia-specific cytotoxic T lymphocytes (CTLs) became exhausted. They maintained only limited cytotoxic activity, and did not produce interferon-gamma or tumor necrosis factor-alpha or expand after restimulation. CML-specific CTLs were characterized by high expression of programmed death 1 (PD-1), whereas CML cells expressed PD-ligand 1 (PD-L1). Blocking the PD-1/PD-L1 interaction by generating bcCML in PD-1-deficient mice or by repetitive administration of alphaPD-L1 antibody prolonged survival. In addition, we found that PD-1 is up-regulated on CD8(+) T cells from CML patients. Taken together, our results suggest that blocking the PD-1/PD-L1 interaction may restore the function of CML-specific CTLs and may represent a novel therapeutic approach for CML. |
| 巻・号 | 114(8) |
| ページ | 1528-36 |
| 公開日 | 2009-8-20 |
| DOI | 10.1182/blood-2008-09-179697 |
| PII | S0006-4971(20)37178-0 |
| PMID | 19420358 |
| MeSH | Adult Animals Antigens, Surface / genetics Antigens, Surface / metabolism Antigens, Surface / physiology* Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism Apoptosis Regulatory Proteins / physiology* Cells, Cultured Disease Progression Female Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics* Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology* Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology Lymphocyte Count Male Mice Mice, Inbred C57BL Mice, Transgenic Middle Aged Models, Biological Programmed Cell Death 1 Receptor Signal Transduction / genetics Signal Transduction / physiology T-Lymphocytes / pathology* |
| IF | 17.794 |
| 引用数 | 162 |
| WOS 分野 | HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02142 |