CHU Sainte-Justine Research Center, Center of Cancerology Charles-Bruneau, Montreal, Quebec, Canada.
Biol Blood Marrow Transplant. 2013 Sep;19(9):1407-11. doi: 10.1016/j.bbmt.2013.07.007. Epub 2013 Jul 12.
Fas-mediated apoptosis is one of the mechanisms used by tumor cells to escape the cytotoxicity of tumor-infiltrating lymphocytes. It has been suggested that cytokine-induced killer (CIK) cells are resistant to Fas-mediated apoptosis, thereby rendering them more attractive for use in cellular immunotherapy. Unlike what was observed by others, here we show that CIK cells are sensitive to Fas-mediated apoptosis. We have observed an increase in Fas expression in the different CIK cell subpopulations (CD3(+)CD56(-), CD3(+)CD56(+), and CD3(-)CD56(+)) isolated from both cord blood (CB) and peripheral blood (PB). We also show that the bulk, as well as the CD3(+)CD56(-) and CD56(+) CB- and PB-CIK cell subpopulations were sensitive to Fas-mediated apoptosis induced by both CH11 and APO-1 antibodies, albeit with a weaker effect for the CH11 antibody on CB-CIK cells. In addition, in the presence of the APO-1 and CH11 inducers, Fas engagement inhibited the cytotoxic activity of CB- and PB-CIK cells. This new contradictory result may help explain the variable efficacy observed with CIK cells in the clinic.
Fas 介导的细胞凋亡是肿瘤细胞逃避肿瘤浸润淋巴细胞细胞毒性的机制之一。有人认为细胞因子诱导的杀伤（CIK）细胞对 Fas 介导的细胞凋亡具有抗性，从而使其更适合用于细胞免疫治疗。与其他人观察到的不同，我们在这里显示 CIK 细胞对 Fas 介导的细胞凋亡敏感。我们已经观察到从脐带血（CB）和外周血（PB）分离的不同 CIK 细胞亚群（CD3(+)CD56(-)、CD3(+)CD56(+)和 CD3(-)CD56(+))中 Fas 表达增加。我们还表明， bulk 以及 CD3(+)CD56(-)和 CD56(+)CB 和 PB-CIK 细胞亚群对 CH11 和 APO-1 抗体诱导的 Fas 介导的细胞凋亡敏感，尽管 CH11 抗体对 CB-CIK 细胞的作用较弱。此外，在 APO-1 和 CH11 诱导剂存在下，Fas 结合抑制了 CB 和 PB-CIK 细胞的细胞毒性活性。这一新的矛盾结果可能有助于解释临床上观察到的 CIK 细胞疗效的可变性。
