Abstract:
Allogeneic hematopoietic cell transplantation (alloHCT) provides a potential curative treatment for haematological malignancies. The therapeutic Graft-versus-Leukaemia (GvL) effect is induced by donor T cells attacking patient hematopoietic (malignant) cells. However, if healthy non-hematopoietic tissues are targeted, Graft-versus-Disease (GvHD) may develop. After HLA-matched alloHCT, GvL and GvHD are induced by donor T cells recognizing polymorphic peptides presented by HLA on patient cells, so-called minor histocompatibility antigens (MiHAs). The balance between GvL and GvHD depends on the tissue distribution of MiHAs and T-cell frequencies targeting these MiHAs. T cells against broadly expressed MiHAs induce GvL and GvHD, whereas those targeting MiHAs with hematopoietic-restricted expression induce GvL without GvHD. Recently, the MiHA repertoire identified in natural immune responses after alloHCT was expanded to 159 total HLA-I-restricted MiHAs, including 14 hematopoietic-restricted MiHAs. This review explores their potential relevance to predict, monitor, and manipulate GvL and GvHD for improving clinical outcome after HLA-matched alloHCT.
摘要:
异基因造血细胞移植(alloHCT)为血液恶性肿瘤提供了潜在的治愈性治疗。治疗性移植物抗白血病(GvL)效应由供体T细胞攻击患者造血(恶性)细胞诱导。然而,如果健康的非造血组织成为目标,移植物抗疾病(GvHD)可能发展。HLA匹配的alloHCT后,GvL和GvHD由识别患者细胞上HLA呈递的多态肽的供体T细胞诱导,所谓的次要组织相容性抗原(MiHA)。GvL和GvHD之间的平衡取决于MiHA的组织分布和靶向这些MiHA的T细胞频率。针对广泛表达的MiHAs的T细胞诱导GvL和GvHD,而那些靶向具有造血限制表达的MiHA的诱导GvL而没有GvHD。最近,alloHCT后在天然免疫反应中鉴定的MiHA库扩展到159个HLA-I限制性的总MiHA,包括14个限制造血的MiHAs.这篇综述探讨了它们与预测的潜在相关性,监视器,并操纵GvL和GvHD以改善HLA匹配的alloHCT后的临床结果。