Gress Ronald E, Komanduri Krishna V, Einsele Hermann, Cooper Laurence J N
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Biol Blood Marrow Transplant. 2007 Jan;13(1 Suppl 1):17-22. doi: 10.1016/j.bbmt.2006.10.012.
Allogeneic HSCT is the most reliable, robust, and effective cell-based biotherapy currently available to pediatric and adult patients with hematologic malignancies. The central role of donor-derived lymphocytes in mediating an effective antitumor effect, preventing and controlling opportunistic infections, and causing GVHD is well documented in animal experiments and human trials. The profound lymphopenia after conditioning regimens coupled with molecular tools to distinguish host versus donor cells provides investigators a window into immune recovery after allogeneic HSCT. Serial analyses of T cell subsets linking immunophenotype with function have revealed the kinetics of donor-derived T cell recovery after allografting and provided insights into ways the immune system can be manipulated to augment the graft-versus-tumor (GVT) effect without inducing GVHD. As this review demonstrates, investigators are not limited to being passive observers of this immune reconstitution; rather, we have an opportunity to shape the allografted T cells repertoire to selectively augment immune function.
异基因造血干细胞移植(HSCT)是目前儿科和成人血液系统恶性肿瘤患者可获得的最可靠、最强大且最有效的细胞疗法。供体来源的淋巴细胞在介导有效的抗肿瘤作用、预防和控制机会性感染以及引发移植物抗宿主病(GVHD)方面的核心作用在动物实验和人体试验中已有充分记录。预处理方案后的严重淋巴细胞减少,再加上区分宿主细胞与供体细胞的分子工具,为研究人员提供了一个了解异基因造血干细胞移植后免疫恢复情况的窗口。将免疫表型与功能联系起来的T细胞亚群的系列分析揭示了移植后供体来源T细胞恢复的动力学,并为在不诱导移植物抗宿主病(GVHD)的情况下操纵免疫系统以增强移植物抗肿瘤(GVT)效应的方法提供了见解。正如本综述所示,研究人员并不局限于对这种免疫重建进行被动观察;相反,我们有机会塑造同种异体移植T细胞库,以选择性增强免疫功能。