CHU Sainte-Justine Research Center, Center of Cancerology Charles-Bruneau, Montreal, Quebec, Canada; Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
CHU Sainte-Justine Research Center, Center of Cancerology Charles-Bruneau, Montreal, Quebec, Canada.
Cytotherapy. 2014 Jun;16(6):845-56. doi: 10.1016/j.jcyt.2013.12.010. Epub 2014 Feb 12.
Cytokine-induced killer (CIK) cells ex vivo-expanded from cord blood (CB) or peripheral blood (PB) have been shown to be cytotoxic against autologous and allogeneic tumor cells. We have previously shown that CD56(+) CIK cells (CD3(+)CD56(+) and CD3(-)CD56(+)) are capable of killing precursor B-cell acute lymphoblastic leukemia (B-ALL) cell lines. However, the lytic pathways used by CD56(+) PB and CB-CIK cells to kill B-ALL cell lines have not been studied.
CB and PB-CIK cells were differentiated. CD56(+) CB- and PB-CIK cells were compared for expression of different phenotypic markers and for the lytic pathways used to kill B-ALL cell lines.
We found that cytotoxic granule proteins were expressed at higher levels in CD56(+) PB-CIK than in CD56(+) CB-CIK cells. However, CD56(+) CB-CIK cells expressed more tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) compared with CD56(+) PB-CIK cells. We observed that CD56(+) CB-CIK cells used both the NKG2D and TRAIL cytotoxic pathways and were more effective at killing REH cells than CD56(+) PB-CIK cells that used only the NKG2D pathway. In contrast, CD56(+) PB-CIK cells used both NKG2D and TRAIL pathways to kill NALM6 cells, whereas CD56(+) CB-CIK cells used only the NKG2D pathway.
Our results suggest that both the source of CIK and the type of B-ALL cell line have an impact on the intensity of the cytolytic activity and on the pathway used. These findings may have clinical implications with respect to optimizing therapeutic efficacy, which may be dependent on the source of the CIK cells and on the target tumor cells.
从脐带血 (CB) 或外周血 (PB) 体外扩增的细胞因子诱导的杀伤 (CIK) 细胞已被证明对自体和同种异体肿瘤细胞具有细胞毒性。我们之前已经表明，CD56(+)CIK 细胞（CD3(+)CD56(+)和 CD3(-)CD56(+)）能够杀死前体 B 细胞急性淋巴细胞白血病 (B-ALL) 细胞系。然而，CD56(+)PB 和 CB-CIK 细胞用于杀死 B-ALL 细胞系的裂解途径尚未研究。
分化 CB 和 PB-CIK 细胞。比较 CD56(+)CB 和 PB-CIK 细胞表达不同的表型标记物以及用于杀伤 B-ALL 细胞系的裂解途径。
我们发现 CD56(+)PB-CIK 中的细胞毒性颗粒蛋白表达水平高于 CD56(+)CB-CIK 细胞。然而，与 CD56(+)PB-CIK 细胞相比，CD56(+)CB-CIK 细胞表达更多的肿瘤坏死因子相关凋亡诱导配体 (TRAIL)。我们观察到 CD56(+)CB-CIK 细胞使用 NKG2D 和 TRAIL 细胞毒性途径，并且比仅使用 NKG2D 途径的 CD56(+)PB-CIK 细胞更有效地杀死 REH 细胞。相比之下，CD56(+)PB-CIK 细胞使用 NKG2D 和 TRAIL 途径杀死 NALM6 细胞，而 CD56(+)CB-CIK 细胞仅使用 NKG2D 途径。
我们的结果表明，CIK 的来源和 B-ALL 细胞系的类型都对细胞溶解活性的强度和所使用的途径有影响。这些发现可能对优化治疗效果具有临床意义，这可能取决于 CIK 细胞的来源和靶肿瘤细胞。
