The CD70-CD27 pathway is essential for stimulation of a cytotoxic T-cells against acute lymphoblastic leukemia (ALL) cells

In vivo, the T-cell stimulatory capacity of acute lymphoblastic B-cells is poor which has been attributed to low levels of costimulatory surface molecules. CD40-stimulation of B-ALL cells leads to significant upregulation of CD80, CD86 as well as CD70 enhancing allogeneic T-cell-proliferative responses >3fold (n=18). Blockade experiments showed that in the induction of T-cell proliferation CD80/CD86 and CD70 act synergistically. With the aim to generate ALL-specific cytotoxic T cells, CD40-activated blasts of 3 pts were used for stimulation of HLA-matched donor T-cells. CD70 proved critical for CTL generation, as blockade of CD70 inhibited T-cell expansion. In contrast, after stimulation with CD40-activated blasts T-cells exhibited 30–45% specific lysis of naive ALL-cells. These results demonstrate that the CD70-CD27 pathway is a prerequisite for generation of ALL-specific CTLs.