CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Influence of KIR Gene Polymorphisms and KIR-ligand Binding on Outcomes in Hematologic Malignancies following Haploidentical Stem Cell Transplantation: A Comprehensive Review.
The Influence of KIR Gene Polymorphisms and KIR-ligand Binding on Outcomes in Hematologic Malignancies following Haploidentical Stem Cell Transplantation: A Comprehensive Review.
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自然杀伤(NK)细胞的行为和功能受由大量活化和抑制性受体产生的阴性或阳性信号之间的平衡所控制,这些受体包括杀伤细胞免疫球蛋白样受体(KIR)蛋白,它是先天免疫系统的主要组成部分,通过产生细胞因子的释放和细胞毒性,参与对病毒感染转化细胞的初始应答。可以确定的是,KIR在遗传上具有多态性,个体内KIR多样性的程度可能对造血干细胞移植(HSCT)的结局具有潜在影响。在这方面,近期研究表明,KIR与其配体(HLA)在恶性疾病的干细胞移植中同样至关重要。
然而,与HLA表位错配——已知的NK同种反应性原因——不同,对KIR基因在HSCT中作用的完整理解仍不明确。由于个体间KIR基因内容、等位基因多态性和细胞表面表达的遗传变异性,基于HLA和KIR谱系进行合适的供者选择对于改善干细胞移植结局至关重要。
此外,KIR/HLA相互作用对HSCT结局的影响需要更全面地研究。本工作旨在综述NK细胞再生、KIR基因多态性以及KIR-配体结合对单倍体相合干细胞移植后血液系统恶性肿瘤结局的影响。从文献中收集的综合数据可为KIR匹配状态在移植中的意义提供新的见解。
Natural killer (NK) cell behavior and function are controlled by a balance between negative or positive signals generated by an extensive array of activating and inhibiting receptors, including killer cell immunoglobulin-like receptor (KIR) proteins, main components of the innate immune system that contribute to initial responses against viral infected-transformed cells through generation of the release of cytokines and cytotoxicity.
What is certain is that KIRs are genetically polymorphic and the extent of KIRs diversity within the individuals may have the potential outcomes for hematopoietic stem cell transplantation (HSCT). In this regard, recent studies suggest that KIR is as imperative as its ligand (HLA) in stem cell transplantation for malignant diseases.
However, unlike HLA epitope mismatches, which are well-known causes of NK alloreactivity, a complete understanding of KIR genes' role in HSCT remains unclear. Because of genetic variability in KIR gene content, allelic polymorphism, and cell-surface expression among individuals, an appropriate selection of donors based on HLA and KIR profiles is crucial to improve outcomes of stem cell transplantation.
In addition, the impact of the KIR/HLA interaction on HSCT outcomes needs to be investigated more comprehensively. The present work aimed to review the NK cell regeneration, KIR gene polymorphisms, and KIRligand binding on outcomes in hematologic malignancies following haploidentical stem cell transplantation. Comprehensive data gathered from the literature can provide new insight into the significance of KIR matching status in transplantations.
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