| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
Induction of γδT Cells Using Zoledronate Plus Interleukin-2 in Patients with Metastatic Cancer |
|
言語 |
en |
| 作成者 |
Nagamine, Ichiro
Yamaguchi, Yoshiyuki
Ohara, Masahiro
Ikeda, Takuhiro
Okada, Morihito
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
(c) Hiroshima University Medical Press. |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
γδT cells |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Zoledronate |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Interleukin-2 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Adoptive immunotherapy |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Cancer |
| 主題 |
|
|
主題Scheme |
NDC |
|
主題 |
490 |
| 内容記述 |
|
|
内容記述 |
A loss of human leukocyte antigen (HLA) expression in clinical tumors is one of their escape mechanisms from immune attack by HLA-restricted effector cells. In this study, the induction of HLA-unrestricted effector cells, γδT cells, using zoledronate (ZOL) and interleukin (IL)-2 in vitro was investigated in patients with metastatic cancer. Peripheral blood mononuclear cells (PBMCs) from 10 cancer patients (8 colorectal and 2 esophageal) with multiple metastases and ascites lymphocytes from 3 cancer patients (1 gastric and 2 colorectal) were stimulated with varied concentrations of ZOL plus 100 U/ml IL-2 for 48 hr followed by culturing with IL-2 alone for 12 days. Lymphocyte proliferative responses were determined using 3H-TdR uptakes and interferon (IFN)-γ production was evaluated using enzyme-linked immunosorbent assay. Surface phenotyping was performed using flow cytometry. Cytotoxic activity of effector cells was determined using 51Cr-releasing assay. It was found that proliferative responses of PBMCs were significantly stimulated with ZOL plus IL-2 when compared with IL-2 alone, showing 200 to 500-fold expansions for 2 weeks, although ZOL alone induced no response. The optimal concentration of ZOL was 1-5 μM. Ascites lymphocytes could also be stimulated with ZOL plus IL-2. The proliferative responses were remarkable in patients whose PBMCs could produce high levels ofIFN-γ during an initial 48-hr stimulation using ZOL plus IL-2. Removal of an adherent cell fraction before the induction augmented the proliferative responses in patients who otherwise had low-grade proliferative responses. Generated cells comprising approximately 90 or 20% in PBMCs from healthy donors or cancer patients, respectively, expressed γδ-type T-cell receptor. γδT cells showed high cytotoxic activity against CD166-positive TE12 and TE13 cancer cells but not against CD166-negative MKN45 cells. The cytotoxic activity against TE13 cells was augmented when target cells were pre-treated overnight with ZOL. These results suggest that ZOL in the presence of IL-2 can efficiently stimulate the proliferation of γδT cells, which have cytotoxic properties against cancer cells. The use of zoledronate-activated killer (ZAK) cells should be encouraged in possible adoptive immunotherapy trials for patients with incurable cancer. |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
Hiroshima University Medical Press |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
departmental bulletin paper |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0018-2052 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00664312 |
| 開始ページ |
|
|
開始ページ |
37 |
| 書誌情報 |
Hiroshima Journal of Medical Sciences
Hiroshima Journal of Medical Sciences
巻 58,
号 1,
p. 37-44,
発行日 2009-03
|
| 旧ID |
34964 |
HiroshimaJMedSci_58_37.pdf (1.8 MB)
