CD137 enhances cytotoxicity of CD3(+)CD56(+) cells and their capacities to induce CD4(+) Th1 responses.
CD137 enhances cytotoxicity of CD3(+)CD56(+) cells and their capacities to induce CD4(+) Th1 responses.
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CD137 增强 CD3( )CD56( ) 细胞的细胞毒性及其诱导 CD4( ) Th1 反应的能力。
DOI：
10.1016/j.biopha.2008.10.003
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发表时间：
2009-08
期刊：
影响因子：
--
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中科院分区：
文献类型：
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CD137(4-1BB)是一个TNFR超家族成员，介导共刺激信号导致T细胞和NK细胞的增殖和细胞因子的产生，但CD137信号对CD3+CD56+细胞亚群的影响尚未得到很好的报道。本研究旨在探讨CD137信号在CD3+CD56+细胞功能调节中的作用。在CIK细胞培养中加入抗CD137单抗或小鼠IgG1同型对照，观察其对CD3+CD56+细胞的增殖和抗肿瘤作用。我们观察到抗CD137单抗能显著促进CIK细胞的增殖。CD137-CIK细胞和其中的CD3+CD56+细胞亚群对肿瘤细胞株A549具有较强的杀伤能力。移植A549细胞和CD137-CIK细胞治疗的SCID小鼠存活时间延长。进一步研究发现CD137-CIK细胞中CD3+CD56+细胞比例显著升高。CD137-CIK细胞CD3+CD56+细胞表达NKG2D上调。CD13 7-γ+CD5 6+细胞表达干扰素-α、IL-2和肿瘤坏死因子-β显著增加，而产生转化生长因子-CIK 1、IL-4和IL-10减少。此外，抗CD137单抗还能提高CD3+CD56+细胞诱导CD4+Th1反应的能力。我们进一步表明，抗CD137单抗对非小细胞肺癌患者外周血中CD3+CD56+细胞也有同样的作用。结论：CD137信号可通过提高CD3+CD56+细胞的比例及其细胞毒作用增强CIK细胞的体内外杀伤肿瘤细胞的能力。此外，CD137信号可增强CD3+CD56+细胞诱导CD4+Th1反应的能力，从而间接增强其抗肿瘤活性。综上所述，我们的研究可以被认为是基于CIK细胞的癌症免疫治疗的有价值的。
CD137 (4-1BB) is a TNFR superfamily member that mediates the costimulatory signal resulting in T cells and NK cells proliferation and cytokines production, but the effects of CD137 signaling on CD3+CD56+cell subpopulation have not been well-documented. The aim of this study was to investigate the effects of CD137 signaling on regulation of CD3+CD56+cell function. Anti-CD137 mAb or mouse IgG1 isotype control was added to CIK cell culture to determine the effects of proliferation and anti-tumor effects on CD3+CD56+cells. We observed that anti-CD137 mAb could dramatically promote proliferation of CIK cells. And CD137–CIK cells and CD3+CD56+cell subpopulation within them possessed higher ability to kill tumor cell line A549. The SCID mice engrafted with A549 cells and treated with CD137–CIK cells have prolonged survival. Further studies revealed that the percentages of CD3+CD56+cells were elevated significantly in CD137–CIK cells. The expression of NKG2D was up-regulated on CD3+CD56+cells from CD137–CIK cells. The expression of IFN-γ, IL-2 and TNF-α increased significantly whereas the production of TGF-β1, IL-4 and IL-10 decreased in CD3+CD56+cells from CD137–CIK cells. In addition, anti-CD137 mAb can elevate the capacity of CD3+CD56+cells to induce CD4+Th1 responses. We further showed that the anti-CD137 mAb also had the same effects on CD3+CD56+cells expanded from the PBMCs of patients with NSCLC. We concluded that CD137 signaling could enhance the abilities of CIK cells to kill tumor cells in vitro and in vivo via increasing the proportion of CD3+CD56+cells and their cytotoxicity. Furthermore, CD137 signaling can elevate the capacity of CD3+CD56+cells to induce CD4+Th1 responses which may enhance their anti-tumor activity indirectly. Taken together, our studies could be considered as valuable in CIK cells-based cancer immunotherapy.
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DOI：
10.1016/0022-1759(79)90166-2
发表时间：
1979-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
R. Baskin;S. Hanna
通讯作者：
R. Baskin;S. Hanna
影响因子：
4.4
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P. Olioso;R. Giancola;M. Riti;P. Accorsi;A. Spadano;D. Natale;Roberto Rossetti;P. Bartolomeo;A. Iacone
影响因子：
4.4
作者：
P. Lu;R. Negrin
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P. Lu;R. Negrin
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0.8
作者：
Chien-Feng C. Sun;Yi-Yueh Hsieh;K. Ngan;Wei-Ting Wang
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Chien-Feng C. Sun;Yi-Yueh Hsieh;K. Ngan;Wei-Ting Wang