肿瘤细胞治疗研究
英文原题：Natural killer cells adopt an activated and decidual-like phenotype after autologous hematopoietic stem cell transplantation in children with cancer.
我们的发现为 autoHSCT 后免疫系统重建期间 NK 细胞的病理生理学提供了有价值的见解，并可能有助于儿童癌症的管理。
背景：自体造血干细胞移植（autoHSCT）后，NK细胞是最早恢复的免疫细胞群之一，但其在儿科患者中的动态功能研究不足。研究NK细胞恢复可能有助于深入理解autoHSCT后的免疫重建并优化临床结局。方法：我们表征了13名患不同肿瘤的儿童（男性8名，女性5名，年龄3–11岁）在autoHSCT前及移植后最多6个月的NK细胞。开展多参数流式细胞术分析并测定血浆细胞因子水平。另纳入8名成年健康供者（男性5名，女性3名，年龄25–62岁），开展包括单细胞RNA测序在内的体外实验，以阐明autoHSCT后NK细胞库的变化。结果：关键发现是移植后早期出现短暂的蜕膜样NK细胞表型。这些细胞未成熟且处于活化状态，抑制性受体表达升高，活化受体水平降低。该活化、蜕膜样表型以CD56、CD9、CD49a、CD151、CD38、HLA-DR和CD55表达升高为特征。多种血浆细胞因子水平与观察到的NK细胞表型变化相关。此外，体外实验重现了autoHSCT后NK细胞的变化。具体而言，结果表明IL-15和TGF-β共同诱导autoHSCT后NK细胞形成这一特异表型。最后，我们在儿科患者队列中观察到，移植后不久复发与CD56dim NK细胞比例呈正相关。结论：总体而言，我们的发现为理解autoHSCT后免疫重建过程中NK细胞的病理生理变化提供了有价值见解，并可能有助于儿童癌症管理。通俗摘要：自体造血干细胞移植（autoHSCT）是一种常见癌症治疗方法，会移植患者自身的血液干细胞。然而，我们尚未充分了解儿童患者接受autoHSCT后的情况。我们发现，癌症患儿接受autoHSCT后，自然杀伤（NK）细胞会迅速发生显著变化。NK细胞暂时表达类似妊娠期细胞的膜蛋白，并变得更加活跃。这些NK细胞表面的受体会调节其功能：活化受体像“启动开关”，抑制性受体像“关闭开关”。变化后，抑制性受体增加，而活化受体减少。这些改变与血液中的某些细胞因子有关。实验室检测显示，IL-15和TGF-β两种分子共同导致NK细胞发生这些变化。了解这些改变可能有助于改善儿童autoHSCT后的治疗和照护。
BACKGROUND: Natural killer (NK) cells are among the first immune cell populations to recover after autologous hematopoietic stem cell transplantation (autoHSCT ), yet their dynamic function in pediatric patients remains understudied. Investigating NK cell recovery could improve understanding of post-autoHSCT immune reconstitution and optimize clinical outcomes. METHODS: We characterized NK cells in 13 children (male: 8; female: 5; age range: 3-11 years) with various tumors before and up to 6 months after autoHSCT. Multiparametric flow cytometry analyses and plasma cytokine level determinations were performed. In vitro experiments, including single-cell RNA sequencing, were conducted to elucidate post-autoHSCT changes in the NK cell repertoire using 8 adult healthy donors (male: 5; female: 3; age range: 25-62 years). RESULTS: Key findings highlight a transient decidual-like NK cell phenotype emerging early post-transplant. These cells are immature and activated, with increased inhibitory receptor expression and diminished activating receptor levels. This activated and decidual-like phenotype is characterized by elevated expression of CD56, CD9, CD49a, CD151, CD38, HLA-DR, and CD55. Plasma levels of several cytokines are associated with the observed changes in NK cells' phenotype. In addition, in vitro experiments recapitulate the alterations observed in NK cells shortly after autoHSCT. Specifically, results demonstrate that the combination of IL-15 and TGF- induces this distinctive phenotype on NK cells after autoHSCT. Finally, we observe a positive correlation between relapse and the percentage of CD56 dim NK cells shortly after autoHSCT in our cohort of pediatric patients. CONCLUSIONS: Altogether, our findings provide valuable insights into the physiopathology of NK cells during immune system reconstitution after autoHSCT and can potentially help in the management of cancer in children. Autologous hematopoietic stem cell transplantation (autoHSCT) is a common cancer treatment that transplants a patient s own blood stem cells. However, the autoHSCT function in pediatric patients is not fully understood. Here, we find that natural killer (NK) cells, which help fight cancer, change significantly right after autoHSCT in children with cancer. NK cells temporarily express cell membrane proteins similar to those found in pregnancy and become more active. These NK cells show membrane proteins called receptors that modify their function: activating or inhibiting them. Their inhibitory receptors (off switches) increase, while activating receptors (on switches) decrease. These modifications are linked to certain molecules in the blood called cytokines. Lab tests show that two molecules, IL-15 and TGF- , together cause these alterations in NK cells. Understanding these changes may help improve treatment and care for children after autoHSCT treatment.
MEMBER ACCOUNT
登录成功会直接打开下一页。
