| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC02142 |
