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:Use of cytokine-induced killer cell therapy in patients with colorectal cancer: a systematic review and meta-analysis.
Use of cytokine-induced killer cell therapy in patients with colorectal cancer: a systematic review and meta-analysis.
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与标准治疗相比,接受额外 CIK 细胞治疗的患者获得了良好的结局,且未增加毒性,值得进一步研究 CIK 疗法用于 CRC 的治疗。
评估细胞因子诱导的杀伤细胞(CIK)疗法(一种过继性免疫疗法)对结直肠癌(CRC)获益的临床研究数量正在增加。在许多此类试验中,CIK疗法与常规癌症治疗联合给药。本综述的目的是通过meta分析系统评估关于CIK疗法用于CRC管理的现有文献(其中大多数仅以中文发表),并确定与CIK疗法成功实施相关的参数。
通过电子检索MEDLINE、Embase、中国知网和万方数据数据库,查找比较CIK治疗与非CIK治疗在CRC患者中应用的前瞻性和回顾性临床研究。使用HR和相对危险度(RR)对总生存期(OS)、无进展生存期(PFS)、OS率和PFS率、总缓解率(ORR)及毒性等临床终点进行meta分析,并针对研究设计、疾病分期、联合治疗类型和给药时机,采用卡方(χ2)检验和I平方(I2)统计量进行亚组分析。
共纳入70项研究,涉及6743例患者。CIK治疗在OS(HR=0.59,95% CI:0.53至0.65)、PFS(HR=0.55,95% CI:0.47至0.63)和ORR(RR=0.65,95% CI:0.57至0.74)方面优于非CIK治疗,且未增加毒性(HR=0.59,95% CI:0.16至2.25)。按研究设计(随机与非随机研究设计)、疾病分期(I-III期与IV期)、与树突状细胞(DCs)联合治疗(CIK与DC-CIK治疗)或治疗给药时机(与联合抗癌治疗同步与序贯)对OS和PFS进行的亚组分析也显示,CIK治疗的临床获益在任何亚组分析中均稳健。此外,与DCs联合治疗并未较单纯CIK治疗改善临床结局。
The number of clinical studies evaluating the benefit of cytokine-induced killer cell (CIK) therapy, an adoptive immunotherapy, for colorectal cancer (CRC) is increasing. In many of these trials, CIK therapy was coadministered with conventional cancer therapy. The aim of this review is to systematically assess the available literature, in which the majority were only in Chinese, on CIK therapy for the management of CRC using meta-analysis and to identify parameters associated with successful CIK therapy implementation.
Prospective and retrospective clinical studies which compared CIK therapy to non-CIK therapy in patients with CRC were searched for electronically on MEDLINE, Embase, China National Knowledge Infrastructure, and Wanfang Data databases. The clinical endpoints of overall survival (OS), progression-free survival (PFS), OS and PFS rates, overall response rate (ORR), and toxicity were meta-analyzed using HR and relative ratio (RR), and subgroup analyses were performed using chi-square (χ 2 ) test and I-squared (I 2 ) statistics for study design, disease stage, cotherapy type, and timing of administration.
In total, 70 studies involving 6743 patients were analyzed. CIK therapy was favored over non-CIK therapy for OS (HR=0.59, 95% CI: 0.53 to 0.65), PFS (HR=0.55, 95% CI: 0.47 to 0.63), and ORR (RR=0.65, 95% CI: 0.57 to 0.74) without increasing toxicity (HR=0.59, 95% CI: 0.16 to 2.25). Subgroup analyses on OS and PFS by study design (randomized vs non-randomized study design), disease stage (Stage I-III vs Stage IV), cotreatment with dendritic cells (DCs) (CIK vs DC-CIK therapy), or timing of therapy administration (concurrent vs sequential with coadministered anticancer therapy) also showed that the clinical benefit of CIK therapy was robust in any subgroup analysis. Furthermore, cotreatment with DCs did not improve clinical outcomes over CIK therapy alone.
Compared with standard therapy, patients who received additional CIK cell therapy had favorable outcomes without increased toxicity, warranting further investigation into CIK therapy for the treatment of CRC.
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