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:Autologous ex vivo expanded NK cells combined with PD-1 inhibitor improved ascitic fluid immune microenvironment of peritoneal metastatic pancreatic cancer: a case study.
Autologous ex vivo expanded NK cells combined with PD-1 inhibitor improved ascitic fluid immune microenvironment of peritoneal metastatic pancreatic cancer: a case study.
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胰腺癌患者出现腹膜转移与不良预后相关。化疗和放疗可能导致胰腺癌患者预后不良。然而,免疫治疗即使在疾病晚期也能改善预后。本研究报道了一例自体体外扩增自然杀伤(NK)细胞联合程序性细胞死亡1(PD-1)抑制剂治疗胰腺癌伴腹膜转移患者的病例。NK细胞经体外扩增后静脉输注,随后静脉给予两剂PD-1抑制剂。联合治疗前后进行计算机断层扫描和磁共振成像以评估肿瘤大小。
此外,联合治疗前后采集血液样本和腹水进行分析。采用流式细胞术检测采集腹水中T细胞和巨噬细胞的亚群。同时,通过酶联免疫吸附试验对腹水中细胞因子水平进行定量,并对上清液进行Luminex检测。
结果显示,联合治疗后腹水中癌细胞消失,T细胞被激活,这可通过PD-1和T细胞免疫球蛋白及黏蛋白结构域包含蛋白3水平下降得到证实。
此外,巨噬细胞功能改善,表现为CD86水平升高以及CD206和HLA-DR水平降低。值得注意的是,联合治疗后腹水中细胞因子(转化生长因子-β、血管内皮生长因子和白细胞介素-10)水平显著上调。
总之,NK细胞联合PD-1抑制剂可改善腹腔内癌病的免疫微环境。因此,联合治疗可能有利于抑制胰腺癌及腹腔内转移灶的存在。然而,仍需进一步开展随机研究以确认联合治疗的疗效。
The presence of peritoneal metastasis in patients with pancreatic cancer is associated with poor prognosis. Chemotherapy and radiotherapy may result in poor prognosis in patients with pancreatic cancer.
However, immunotherapy improves prognosis even at an advanced stage of the disease. The present study reported a case of a combined therapy of autologous ex vivo expanded natural killer (NK) cells and programmed cell death 1 (PD-1) inhibitor in a patient with pancreatic cancer and peritoneal metastasis.
The NK cells were expanded ex vivo and intravenously injected. This was followed by intravenous administration of two dosages of PD-1 inhibitor. Computed tomography and magnetic resonance imaging were performed to assess the size of tumor before and after the combined therapy.
In addition, the blood sample and ascites were collected and analyzed before and after the combined therapy. Flow cytometry was carried out to measure the subsets of T cells and macrophages in the collected ascites. Meanwhile, the levels of cytokines in the ascites were quantified through enzyme-linked immunosorbent assay, and Luminex assays were conducted on the supernatant.
It was revealed that after the combined therapy, cancer cells disappeared in the ascites, and the T cells were activated, which could be confirmed by the decreased levels of PD-1 and T cell immunoglobulin and mucin domain-containing protein 3. Also, the functioning of macrophages was improved, as shown by the increased level of CD86 and the reduced levels of CD206 and HLA-DR.
Notably, the levels of cytokines (transforming growth factor-β, vascular endothelial growth factor, and interleukin-10) in ascites were significantly upregulated after the combined therapy.
In conclusion, it was evident that NK cells combined with PD-1 inhibitor improved the immune microenvironment of carcinomatosis in the peritoneal cavity.
Therefore, the combined therapy may be beneficial for suppressing pancreatic cancer and the presence of metastases in the peritoneal cavity.
However, there is a need for additional randomized studies to confirm the efficacy of combined therapy.
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