Ex vivo expanded human Vγ9Vδ2+γδ-T cells mediate innate antitumor activity against human prostate cancer cells in vitro
Ex vivo expanded human Vγ9Vδ2+γδ-T cells mediate innate antitumor activity against human prostate cancer cells in vitro
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DOI：
10.1097/01.ju.0000154355.45816.0b
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发表时间：
2005-05-01
影响因子：
6.6
通讯作者：
Lopez, RD
中科院分区：
文献类型：
--
作者：
Liu, ZY;Guo, BL;Lopez, RD
目的：我们以前已经确定了一个CD 2介导的，白细胞介素-12依赖性信号传导途径，抑制激活诱导的细胞死亡的有丝分裂原刺激的人γ δ-T细胞，允许这些细胞的大规模扩增。在此，我们报告的先天抗肿瘤活性的扩大人V γ 9V δ 2+ γ δ-T细胞对人前列腺癌cells.Materials and Methods：抗凋亡的人γ δ-T细胞在体外扩增培养的人外周血单个核细胞，然后富集到高纯度的免疫磁性分离。在体外细胞毒性的扩增γ δ-T细胞对人前列腺癌细胞系使用标准的细胞毒性assays.Results：γ δ-T细胞来源于各种捐助者一致显示裂解活性对前列腺癌细胞系DU-145和PC-3，但不是LNCaP。针对V γ 9或V δ 2 T细胞受体链的mAb以及针对细胞间粘附分子-1（ICAM-1）或CD 18（ICAM-1反受体的β亚基）的mAb阻断γ δ T细胞介导的前列腺癌细胞杀伤。结论：体外扩增的人V γ 9V δ 2+ γ δ-T细胞能够在体外天然识别和杀伤某些人前列腺肿瘤细胞系。前列腺癌细胞的识别和杀伤以γ δ-T细胞受体依赖性方式发生，并且似乎还涉及ICAM-1和CD 18之间的相互作用。因为抗凋亡的人V-γ 9V δ 2+ γ δ-T细胞可以容易地扩增到大量（临床规模），所以必须在开发过继免疫治疗策略以利用γ δ-T细胞对前列腺癌的先天免疫应答的背景下考虑这些发现。
Purpose: We have previously identified a CD2 mediated, interleukin-12 dependent signaling pathway that inhibits activation induced cell death in mitogen stimulated human gamma delta-T cells, permitting the large-scale expansion of these cells. Herein we report the innate antitumor activity of expanded human V gamma 9V delta 2+ gamma delta-T cells against human prostate cancer cells.Materials and Methods: Apoptosis resistant human gamma delta-T cells were expanded in vitro from cultured human peripheral blood mononuclear cells and then enriched to high purity by immunomagnetic separation. In vitro cytotoxicity of expanded gamma delta-T cells was measured against human prostate cancer cell lines using standard cytotoxicity assays.Results: gamma delta-T cells derived from various donors consistently showed lytic activity against the prostate cancer cell lines DU-145 and PC-3 but not LNCaP. mAbs against V gamma 9 or V delta 2 T-cell receptor chains as well as mAb against intercellular adhesion molecule-1 (ICAM-1) or CD18, the beta subunit of ICAM-1 counter receptors, blocked gamma delta-T cell mediated killing of prostate cancer cells. gamma delta-T cells lysed prostate cancer cell lines largely through the perforin/granzyme pathway.Conclusions: Ex vivo, expanded human V gamma 9V delta 2+ gamma delta-T cells are able innately to recognize and kill certain human prostate tumor cell lines in vitro. The recognition and killing of prostate cancer cells occurs in a gamma delta-T-cell receptor dependent manner and it also appears to involve interactions between ICAM-1 and CD18. Because apoptosis resistant human V-gamma 9V delta 2+ gamma delta-T cells can readily be expanded to large numbers (clinical scale), these findings must be considered in the context of developing adoptive immunotherapy strategies to exploit gamma delta-T cell innate immune responses to prostate cancer.