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用源自晚期癌症患者的 CEA 肽脉冲γδ T 细胞诱导细胞毒性 T 淋巴细胞。

Induction of cytotoxic T lymphocytes by CEA peptide-pulsed γδ T-cells isolated from patients with advanced cancer.

机构信息

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

出版信息

Anticancer Res. 2011 Jul;31(7):2419-24.

Abstract

Cytotoxic γδ T-cells recognize antigens directly without the need for antigen processing and presentation. Recently, it was reported that they can also present antigens and proliferate in vitro. In this study, we examined whether γδ T-cells isolated from patients with advanced cancer can be used for immunotherapy. Twenty-two inoperable patients with multiple cancer metastases were enrolled in the study. There was no significant difference in the ratio of γδ T-cells within the peripheral blood mononuclear cell population isolated from healthy volunteers and cancer patients. γδ T-Cells isolated from cancer patients were expanded 2- to 5-fold using zoledronic acid or 2-methyl-3butenyl-1-pyrophosphate and IL-2. Autologous CD8(+) T-cells co-cultured with expanded CEA peptide-pulsed γδ T-cells from cancer patients with HLA-A24 killed more CEA-positive HLA-A24-matched gastric cancer cells and secreted higher levels of interferon-γ. These results suggest that γδ T-cells from cancer patients may be ideal candidates for adoptive immunotherapy.

摘要

细胞毒性 γδ T 细胞无需抗原加工和呈递即可直接识别抗原。最近有报道称,它们还可以在体外呈递抗原并增殖。在这项研究中,我们研究了是否可以从晚期癌症患者中分离出 γδ T 细胞用于免疫治疗。本研究纳入了 22 例无法手术的多部位癌症转移患者。从健康志愿者和癌症患者外周血单个核细胞中分离出的 γδ T 细胞在群体中的比例无显著差异。用唑来膦酸或 2-甲基-3-丁烯-1-焦磷酸和 IL-2 可将癌症患者的 γδ T 细胞扩增 2-5 倍。与扩增的 CEA 肽脉冲 γδ T 细胞共培养的自体 CD8(+) T 细胞可杀伤更多 CEA 阳性 HLA-A24 匹配的胃癌细胞,并分泌更高水平的干扰素-γ。这些结果表明,癌症患者的 γδ T 细胞可能是过继免疫治疗的理想候选者。

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