RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Role of NK cells in cord blood transplantation and their enhancement by the missing ligand effect of the killer-immunoglobulin like receptor.
Role of NK cells in cord blood transplantation and their enhancement by the missing ligand effect of the killer-immunoglobulin like receptor.
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自然杀伤(NK)细胞是同种异体造血干细胞移植(HSCT)后最早重建的淋巴细胞。特别是在脐血移植(CBT)中,NK细胞数量的增加可持续很长时间。尽管存在相互矛盾的结果,但许多研究表明,NK细胞的早期重建与良好的CBT结局相关,提示最大化NK细胞功能可能改善CBT结局。杀伤细胞免疫球蛋白样受体(KIR)包括抑制性和刺激性受体,可调节NK细胞活性。由于部分KIR以HLA I类分子作为其配体,在某些CBT病例中NK细胞上的KIR-配体相互作用可能缺失,从而导致NK细胞活化并改变HSCT结局。
因此,各种条件下KIR-配体错配的影响已被广泛研究;然而,结果一直存在争议。在这些研究中,使用最大数量CBT的研究表明,只有当CBT使用甲氨蝶呤进行移植物抗宿主病预防时,HLA-C2(KIR2DL1配体)错配对复发率和总生存期才有有利影响。另一项研究提示,KIR-配体错配参与减少急性髓系白血病的复发,由巨细胞病毒再激活介导。这些结果表明,KIR-配体错配引起的NK细胞活化可能对CBT结局产生有利影响,并可能有助于增强NK细胞功能。
Natural killer (NK) cells are the first lymphocytes reconstituted after allogenic hematopoietic stem cell transplantation (HSCT). Especially, in cord blood transplantation (CBT), the increase in the number of NK cells is sustained for a long period. Although there are conflicting results, many studies show that early reconstitution of NK cells is associated with favorable CBT outcomes, suggesting that maximizing NK cell functions could improve the CBT outcome.
Killer immunoglobulin-like receptors (KIRs) include inhibitory and stimulatory receptors, which can regulate NK-cell activity. Because some of the KIRs have HLA class I as their ligand, the KIR-ligand interaction on NK cells can be lost in some cases of CBT, which results in the activation of NK cells and alters HSCT outcome.
Thus, effects of KIR-ligand mismatch under various conditions have been widely examined; however, the results have been controversial. Among such studies, those using the largest number of CBTs showed that HLA-C2 (KIR2DL1-ligand) mismatches have a favorable effect on the relapse rate and overall survival only when the CBT used methotrexate for graft-versus-host disease prophylaxis.
Another study suggested that KIR-ligand mismatch is involved in reducing the relapse of acute myeloid leukemia, mediated by reactivation of cytomegalovirus. These results indicate that activation of NK cells by KIR-ligand mismatch may have favorable effects on CBT outcomes and could help enhance the NK-cell function.
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