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:Tumour-infiltrating Lymphocytes and Radiation Therapy in Rectal Cancer: Systematic Review and Meta-analysis.
Tumour-infiltrating Lymphocytes and Radiation Therapy in Rectal Cancer: Systematic Review and Meta-analysis.
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TILs 是接受根治性治疗(包括 RC 的 RT)患者肿瘤反应和生存结局的有用参数。未来的工作应旨在标准化 TIL 测量和量化方法,并制定方案以阐明这些发现的临床应用。
TIL(肿瘤浸润淋巴细胞)(TILs)是一种有前景的癌症生物标志物。不同的 TILs,包括 CD8+、CD4+、CD3+ 和 FOXP3+,与临床结局相关。然而,关于 TILs 对接受放射治疗(RT)患者的价值尚缺乏数据。我们进行了一项系统性综述和荟萃分析,评估现有数据中 TILs 对接受包括 RT 在内的根治性治疗患者的价值。
符合条件的研究需呈现一个明确界定的患者队列,所有患者均接受了以治愈为目的的治疗,包括 RT,并且还报告了任何 TIL 评分与肿瘤缓解或生存结局之间的关系。在全面检索在线数据库(PubMed、EMBASE、Cochrane 和 Web of Science)后,2 名作者按照系统评价和荟萃分析优先报告条目(PRISMA)指南,对标题、摘要和全文进行了质量和偏倚风险审查。符合质量标准的出版物中的数据按以下方式分组:(1)所分析的 TIL,(2)RT 前或 RT 后 TIL 评估,以及(3)所测量的临床结局。
初步检索共获得669项独特研究。31项研究符合质量标准,其中20项研究直肠癌(RC),4项研究食管癌,3项研究胰腺癌,2项研究肺癌,宫颈癌/子宫癌各1项。我们对RC相关出版物进行了系统评价和meta分析。除2项外,其余均为单机构队列研究。meta分析后,放疗前上皮CD8+(p = 0.04)和间质FOXP3+(p = 0.01)计数与无病生存期相关,而放疗前上皮(p = 0.02)和间质(p = 0.001)FOXP3+ TIL与总生存期相关。放疗后分析中,上皮(p = .04)和间质(p = 0.02)CD8+ TIL与无病生存期相关,上皮CD8+ TIL与总生存期相关(p = 0.01)。术前CD8+和FOXP3+ TIL通常与肿瘤对RT的反应相关,但由于反应测量技术的异质性,未进行meta分析。
Eligible studies presented a defined cohort of patients who all received curative-intent therapy, including RT, and also reported the relationship between any TIL score and either tumour response or survival outcomes. After comprehensive search of online databases (PubMed, EMBASE, Cochrane, and Web of Science), 2 authors conducted title, abstract, and whole-text review for quality and risk of bias following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Data from publications that met quality criteria were grouped via (1) TIL analysed, (2) pre- or post-RT TIL assessment, and (3) clinical outcome measured.
Initial search yielded 669 unique studies. Thirty-one studies met quality criteria, of which 20 studied rectal cancer (RC), 4 oesophageal, 3 pancreas, 2 lung, cervical/uterine 1 each. We conducted systematic review and meta-analysis of the RC publications. All except 2 were single-institutional cohort studies. After meta-analysis, the pre-RT epithelial CD8+ (p = 0.04) and stromal FOXP3+ (p = 0.01) counts were associated with survival without disease, while pre-RT epithelial (p = 0.02) and stromal (p = 0.001) FOXP3+ TILs were associated with overall survival. On post-RT analysis, epithelial (p = .04) and stromal (p = 0.02) CD8+ TILs were associated with survival without disease and epithelial CD8+ TILs were associated with overall survival (p = 0.01).Preoperative CD8+ and FOXP3+ TILs were generally associated with tumour response to RT, but meta-analysis was not conducted due to heterogeneity of response measurement techniques.
TILs represent a useful parameter for tumour response and survival outcomes for patients receiving curative-intent therapy, including RT for RC. Future work should aim to standardise TIL measurement and quantification methods and to develop protocols to clarify clinical application of these findings.
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