Bone marrow mesenchymal stem cells reduce the antitumor activity of cytokine-induced killer/natural killer cells in K562 NOD/SCID mice

Adoptive cellular immunotherapy is an important treatment to eliminate residual tumor cells after hematopoietic stem-cell transplantation. Bone marrow mesenchymal stem cells (MSC) have previously been shown to exert immunoregulation functions, including inhibition of proliferation and killing activities of T cells and natural killer (NK) cells in vitro and reduction of the graft-versus-host disease. MSC can survive in vivo for a long period of time, the influence of MSC on the antitumor activity of subsequently infused immune killer cells is not clear. The aim of this study was to investigate the influences of MSC infused via different paths and at different times on the antitumor activities of cytokine-induced killer (CIK)/NK cells derived from umbilical cord blood in K562 NOD/SCID mice. The potential interaction mechanisms of MSC and CIK/NK cells infused through different paths using different intervals in vivo were subsequently explored. The results show that the antitumor activities of CIK/NK cells was inhibited by MSC when injected via the same path (tail vein), and the suppressive effect of MSC on CIK/NK cells were less pronounced when they were injected separately through different paths. There were no effects of MSC on the antitumor activities of CIK/NK cells if the MSC and CIK/NK cells were injected with a 48-h interval. Moreover, the suppressive effect continuous, even if MSC were infused 48 h earlier than CIK/NK cells. It suggests that pre-injected MSC can reduce the antitumor activities of CIK/NK cells in vivo. The probable mechanisms are that MSC and CIK/NK cells might have a greater opportunity to meet and interact if they are injected simultaneously via the same path. The suppression of MSC on CIK/NK cells in vivo mainly takes place in the reticuloendothelial system, including the lung and the liver.