Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Ann Hematol. 2011 Aug;90(8):873-85. doi: 10.1007/s00277-011-1156-9. Epub 2011 Jan 15.
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.
过继性细胞免疫疗法是消除造血干细胞移植后残留肿瘤细胞的重要治疗方法。骨髓间充质干细胞（MSC）已被证明具有免疫调节功能，包括体外抑制 T 细胞和自然杀伤（NK）细胞的增殖和杀伤活性，以及减少移植物抗宿主病。MSC 可以在体内长期存活，MSC 对随后输注的免疫杀伤细胞的抗肿瘤活性的影响尚不清楚。本研究旨在探讨通过不同途径和不同时间输注 MSC 对脐血来源的细胞因子诱导的杀伤（CIK）/NK 细胞在 K562 NOD/SCID 小鼠中的抗肿瘤活性的影响。随后探讨了体内通过不同途径以不同间隔输注 MSC 和 CIK/NK 细胞的潜在相互作用机制。结果表明，当通过相同途径（尾静脉）注射 MSC 时，CIK/NK 细胞的抗肿瘤活性受到抑制，当通过不同途径分别注射时，MSC 对 CIK/NK 细胞的抑制作用不明显。如果 MSC 和 CIK/NK 细胞注射间隔为 48 小时，则 MSC 对 CIK/NK 细胞的抗肿瘤活性没有影响。此外，即使 MSC 比 CIK/NK 细胞早 48 小时输注，抑制作用也是连续的。这表明预先注射的 MSC 可以降低 CIK/NK 细胞在体内的抗肿瘤活性。可能的机制是，如果通过相同途径同时注射，MSC 和 CIK/NK 细胞可能有更多的机会相遇和相互作用。MSC 对体内 CIK/NK 细胞的抑制主要发生在网状内皮系统，包括肺和肝。
