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:Distinct NK cell function and gene expression in children with acute lymphoblastic leukemia in remission before and after acute exercise: an exploratory study.
Distinct NK cell function and gene expression in children with acute lymphoblastic leukemia in remission before and after acute exercise: an exploratory study.
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急性运动可能改善缓解期 ALL 儿童的 NK 细胞功能,并有望作为 ALL 的辅助治疗。
短时间运动可动员自然杀伤(NK)细胞,并影响成人NK细胞的功能和基因表达。但对于缓解期急性淋巴细胞白血病(ALL)儿童,这些影响尚知之甚少。本研究探讨急性运动对缓解期ALL儿童NK细胞基因表达和细胞毒活性(NKCA)的影响。
9名处于缓解期的B细胞ALL儿童和9名年龄、性别匹配的健康对照(平均年龄分别为14.8±1岁和15±1岁;每组各有2名女孩)完成一次急性运动训练:在峰值功率的60%(相当于峰值摄氧量的71±2%)下骑功率自行车8组,每组2分钟,组间休息1分钟。运动前后检测循环NK细胞基因表达谱(RNA-seq)和NKCA(体外检测)。
基线时,ALL儿童与对照相比有284个基因表达不同;急性运动后,ALL组有179个基因的表达发生不同变化(p<0.01)。基线时有9条NK细胞功能相关通路受影响;运动后有28条炎症反应和癌症相关通路发生变化(FDR<0.05)。IL-2刺激后的NKCA在基线时(p<0.05)及运动后(p=0.09)均低于对照。运动在一定程度上改善了受损活性,但ALL儿童的NKCA仍低于对照。
急性运动可能改善缓解期ALL儿童的NK细胞功能,并有望作为ALL辅助治疗。运动导致的差异性基因表达应答提示,ALL患者的NK细胞可能采用不同的分子策略来应对感染或肿瘤。
Brief bouts of exercise mobilize natural killer (NK) cells and influence their function and gene expression in adults. However, little is known about these effects in children with acute lymphoblastic leukemia (ALL) in remission. This study investigated the effect of acute exercise on NK gene expression and cytotoxic activity (NKCA) in children with ALL in remission.
Nine B-cell ALL children in remission and 9 age- and sex-matched healthy controls (14.8 1 and 15 1 y/o, respectively; 2 girls per group) performed an acute exercise session consisting of eight 2-min bouts of cycle ergometry at 60% of peak work rate (71 2% of peak oxygen uptake) interspersed with 1-min rest intervals. Circulating NK-cell gene expression profile (RNA-seq) and NKCA ( in vitro assay) were studied before and after the exercise session.
At baseline, 284 genes were differently expressed in children with ALL compared to controls, and 179 genes were differently altered by acute exercise in the ALL group (p<0.01). At baseline, nine gene pathways related to NK cell function were affected, while following exercise, 28 pathways associated with inflammatory response and cancer were impacted (FDR<0.05). NKCA following IL-2 stimulation was lower both at baseline (p<0.05) and after exercise (p=0.09) in ALL compared to controls. The impaired activity was partially mitigated following exercise but remained lower in ALL compared to controls.
Acute exercise may improve NK cell function in ALL children in remission and has the potential to be used as adjunctive therapy in ALL. The differential gene expression response to exercise suggests that NK cells in ALL may adopt a different molecular strategy to fight infections or tumors.
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