Murphy W J, Longo D L
NCI-FCRDC, SAIC-Frederick Intramural Research Support Program, MD 21702-1201, USA.
Immunol Rev. 1997 Jun;157:167-76. doi: 10.1111/j.1600-065x.1997.tb00981.x.
Allogeneic bone marrow transplantation (BMT) is being increasingly used for the treatment of a variety of cancers ranging from leukemias to breast cancer. However, significant obstacles currently limit the efficacy of this treatment procedure. The predominant two are the occurrence of graft-versus-host disease (GVHD) and relapse from the cancer. While regimens exist that prevent the occurrence or severity of GVHD, these same regimens also increase the rate of relapse. Conversely, most attempts to reduce the relapse rate also result in increased GVHD. The use of NK cells as an adoptive immunotherapy after BMT is attractive for several reasons. NK cells exhibit antitumor effects both in vitro and in animal models and may, therefore, promote graft-versus-tumor (GVT) effects to remove minimal residual disease after allogeneic BMT. NK cells have also been shown to promote hematopoietic engraftment and donor cell reconstitution after allogeneic BMT in mice. The effects of NK cells on hematopoiesis are believed to be due to the hematopoietic growth factors they can produce after activation. Another advantage in using NK cells is that they can prevent the occurrence of GVHD after allogeneic BMT in mice. This effect is mediated at least in part by the immunosuppressive cytokine, transforming growth factor beta (TGF-beta). BMT studies in mice also indicate that the beneficial effects of NK cells are optimal if they are administered soon after the transplant. Thereafter, NK cells and, more importantly, IL-2, which is used to activate them, are detrimental and can exacerbate the subsequent GVHD. Thus, the use of activated NK cells after allogeneic BMT may provide GVT effects without inducing GVHD.
异基因骨髓移植（BMT）越来越多地用于治疗从白血病到乳腺癌等多种癌症。然而，目前一些重大障碍限制了这种治疗方法的疗效。其中最主要的两个障碍是移植物抗宿主病（GVHD）的发生和癌症复发。虽然存在预防GVHD发生或减轻其严重程度的方案，但这些方案同样会增加复发率。相反，大多数降低复发率的尝试也会导致GVHD增加。BMT后使用自然杀伤细胞（NK细胞）作为过继性免疫疗法具有几个吸引人的原因。NK细胞在体外和动物模型中均表现出抗肿瘤作用，因此可能促进移植物抗肿瘤（GVT）效应，以清除异基因BMT后的微小残留病灶。在小鼠中，NK细胞也已被证明可促进异基因BMT后的造血植入和供体细胞重建。NK细胞对造血的影响被认为是由于其激活后可产生造血生长因子。使用NK细胞的另一个优势是，它们可以预防小鼠异基因BMT后GVHD的发生。这种效应至少部分是由免疫抑制细胞因子转化生长因子β（TGF-β）介导的。小鼠中的BMT研究还表明，如果在移植后不久给予NK细胞，其有益效果最佳。此后，NK细胞，更重要的是用于激活它们的白细胞介素-2，是有害的，会加重随后的GVHD。因此，异基因BMT后使用活化的NK细胞可能在不诱发GVHD的情况下提供GVT效应。
