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:Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models.
Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models.
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卵巢癌(OC)是妇科癌症相关死亡的主要原因。由于该疾病在诊断时通常已出现腹腔内转移,标准治疗可能伴随严重并发症,且疾病复发常见,因此管理仍然具有挑战性。虽然细胞免疫治疗作为有前景的方法正日益受到研究,但最有效的给药途径仍需确定。
我们研究了NK细胞治疗作为一种毒性较低的选项,并考察了永久性NK细胞系NK-92作为合适模型。在此,我们报告了两种使用卵巢腺癌细胞系SKOV-3的异种移植小鼠模型,分别代表早期OC和伴有腹水的晚期OC,以全面评估不同NK-92给药途径的抗癌疗效。采用生物发光成像、IVIS系统细胞追踪和动物生存来评估结果。细胞通过腹腔内(IP)、静脉内(IV)或IP与IV联合途径给药。
我们发现,在早期和已建立的OC异种移植中,NK-92通过IP给药(p = 0.009和p = 0.018)或IP与IV联合给药(p = 0.05和p = 0.017)显著提高了动物生存,而相似剂量的静脉给药与未治疗对照相比对生存无影响(p = 0.665和p = 0.052)。这些发现及我们的新模型,对于增强NK治疗在晚期OC患者中的临床获益具有潜在意义。
Ovarian cancer (OC) is a leading cause of gynecological cancer-related mortality. Management remains challenging as the disease frequently presents with intra-abdominal metastases at diagnosis, standard therapies can be associated with severe complications and disease recurrence is common. While cellular immunotherapy is increasingly investigated as a promising approach, the most effective routes of administration need to be established.
We have investigated NK cell therapeutics as a less toxic option and examined the permanent NK cell line, NK-92, as a suitable model.
Here, we report two xenograft mouse models with the ovarian adenocarcinoma cell line, SKOV-3, representing early-stage OC and late-stage OC with ascites to comprehensively evaluate the anti-cancer efficacy of different routes of NK-92 administration. Bioluminescence imaging, cell tracking with the IVIS system and animal survival were used to evaluate outcomes. The cells were administered via intraperitoneal (IP), intravenous (IV), or a combination of IP and IV routes.
We showed that NK-92 significantly increased animal survival when delivered IP (p = 0. 009 and p = 0. 018) or combined IP and IV (p = 0. 05 and p = 0. 017) in early and established OC xenografts, respectively, whereas intravenous delivery at similar doses had no effect on survival (p = 0. 665 and p = 0. 052) compared with untreated controls.
These findings, and our novel models, have potential implications for enhancing the clinical benefit of NK therapy in patients with advanced OC.
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