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.
英文原题:Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial.
Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
腹腔化疗可提高治疗前肿瘤微环境呈免疫热表型的 EOC 患者的生存率。(日本临床试验注册号,jRCTs031180141。)
iPocc 试验是一项随机、全球性 3 期研究,比较了上皮性卵巢癌(EOC)患者接受腹腔内(IP)和静脉内(IV)卡铂联合剂量密集型紫杉醇化疗的疗效,结果显示接受 IP 化疗的患者无进展生存期改善。本研究旨在探讨预先存在的肿瘤免疫在接受 IP 化疗患者临床结局中的作用。
本研究分析了iPocc试验中的患者数据,选择性纳入原发手术时肿瘤标本得以保存的患者。共116例((IP;n = 59),(IV;n = 57))接受了微阵列分析。采用单样本基因集富集分析评估肿瘤免疫微环境。
在IP组中,肿瘤浸润T细胞、自然杀伤(NK)细胞和细胞毒性淋巴细胞增强的患者,其总生存期(OS)长于IV组,但在低浸润组中则不然。IP治疗改善了CD8A和FOXP3等免疫相关基因高表达患者的OS。根据代表“先天免疫”、“T细胞”、“IFNG反应”和“抑制性分子”的四个参数进行层次聚类分析,将患者分为“免疫热”和“免疫冷”组后,与IV治疗相比,IP治疗显著改善了“免疫热”组的预后,但在“免疫冷”组中则没有。
The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.
This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; n = 59), (IV; n = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment.
Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into "immune Hot" and "immune Cold" groups based on hierarchical clustering analysis using four parameters representing "Innate immunity," "T cells," "IFNG response" and "Inhibitory molecules," IP therapy significantly improved prognosis in the "immune Hot" group, but not in the "immune Cold" group compared to that of IV therapy.
IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment. (Japan Registry of Clinical Trials number, jRCTs031180141.).
MEMBER ACCOUNT
登录成功会直接打开下一页。