MD Anderson Cancer Centre, Houston, TX, USA.
Royal Melbourne Hospital, Melbourne, Australia.
Curr Opin Immunol. 2014 Apr;27:38-45. doi: 10.1016/j.coi.2014.01.010. Epub 2014 Feb 15.
Allogeneic stem cell transplantation (AlloSCT) utilizes HLA-matched donor bone marrow or peripheral blood stem cell grafts to reconstitute haematopoiesis and immunity in patients with bone marrow failure or hematological malignancies. It is now clear that much of the anti-cancer effect of AlloSCT is due to the ability of engrafting donor derived lymphocyte populations to eradicate residual malignant clones, through a phenomenon known as the graft-versus-tumor (GVT) effect. Recognition of the importance of GVT in the long-term control of cancer has allowed substantial reductions in the pre-transplant conditioning intensity, leading to the development of reduced-intensity or even non-myeloablative transplant regimens in some patient groups. These reduced intensity regimens still allow donor cell engraftment and GVT, whilst reducing the morbidity and mortality associated with traditional myeloablative conditioning. Through clinical observations and experimental models of AlloSCT substantial insights have been provided into the mechanisms of immunological control of malignancy even outside the setting of AlloSCT, providing an opportunity to duplicate these anti-cancer mechanisms via non-allogeneic immunotherapies.
异基因造血干细胞移植(AlloSCT)利用 HLA 匹配的供体骨髓或外周血干细胞移植物,在骨髓衰竭或血液系统恶性肿瘤患者中重建造血和免疫功能。现在很清楚,AlloSCT 的大部分抗癌作用是由于植入的供体来源的淋巴细胞群体通过一种称为移植物抗肿瘤(GVT)效应的现象来消除残留的恶性克隆。对 GVT 在癌症长期控制中的重要性的认识,使得移植前预处理强度大大降低,导致在某些患者群体中发展出强度降低甚至非清髓性移植方案。这些降低强度的方案仍然允许供体细胞植入和 GVT,同时降低与传统清髓性预处理相关的发病率和死亡率。通过 AlloSCT 的临床观察和实验模型,即使在 AlloSCT 之外的环境中,也为免疫控制恶性肿瘤的机制提供了实质性的见解,为通过非同种异体免疫疗法复制这些抗癌机制提供了机会。