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:Immune reconstitution in children after haploidentical haematopoietic stem cell transplantation.
Immune reconstitution in children after haploidentical haematopoietic stem cell transplantation.
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与 HLA 相合的 HSCT 相比,接受 PTCy 单倍体相合 HSCT 的儿童患者可能出现免疫重建延迟,且病毒再激活/感染的风险升高。
前瞻性测量 HSCT 前及移植后 1、3、6 和 12 个月的淋巴细胞亚群数量,并在指定时间点测定血液中的巨细胞病毒(CMV)、Epstein-Barr 病毒、腺病毒、BK 病毒(BKV)以及尿液中的腺病毒和 BKV 病毒载量。
单倍体组移植后 1 个月总 T 细胞和辅助性 T 细胞的中位数显著低于 HLA 匹配组。单倍体 HSCT 受者移植后一年内若干 T 细胞亚群及 B 细胞的中位数均显著较低。单倍体组 1 个月时 NK 细胞中位数较低。与 HLA 匹配组相比,单倍体组更常发生 BKV 出血性膀胱炎、血液 CMV 及尿腺病毒再激活。单倍体 HSCT 后接受抗 T 淋巴细胞球蛋白(ATG)的患者,与未接受 ATG 者相比,移植后 1 个月总 T 细胞及 6、12 个月辅助性 T 细胞中位数显著较低,血液 BKV 再激活率较高。
与 HLA 匹配 HSCT 相比,接受 PTCy 单倍体 HSCT 的儿童可能出现免疫重建延迟,并伴随病毒再激活/感染风险升高。在 PTCy 基础上加用 ATG 会延缓 T 细胞恢复并增加 BKV 再激活风险。
We prospectively measured lymphocyte subset numbers before HSCT and at 1, 3, 6 and 12 months after HSCT. Blood cytomegalovirus (CMV), Epstein-Barr virus, adenovirus, BK virus (BKV) and urine adenovirus and BKV viral loads were measured at designated time points.
The median numbers of total T and T helper cells at 1 month were significantly lower in the haploidentical group compared with the HLA-matched group. Haploidentical HSCT recipients had significantly lower median numbers of several T cell subsets and B cells for 1 year after HSCT. The median NK cell count of the haploidentical group was lower at 1 month. BKV haemorrhagic cystitis, blood CMV and urine adenovirus reactivation were more frequently found in the haploidentical group. Post-haploidentical HSCT patients receiving anti-T lymphocyte globulin (ATG) had significantly lower median numbers of total T cells (at 1 month) and T helper cells (at 6 and 12 months) and higher rate of blood BKV reactivation compared with those without ATG.
Paediatric patients who undergo haploidentical HSCT with PTCy are likely to have delayed IR and an increased risk of viral reactivation/infection compared with HLA-matched HSCT. The addition of ATG to PTCy delayed T cell recovery and increased risk of BKV reactivation.
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