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:IMMUNOREACT 0: Biopsy-based immune biomarkers as predictors of response to neoadjuvant therapy for rectal cancer-A systematic review and meta-analysis.
IMMUNOREACT 0: Biopsy-based immune biomarkers as predictors of response to neoadjuvant therapy for rectal cancer-A systematic review and meta-analysis.
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这项 meta 分析表明,高密度 TIL 可能是接受 NT 的直肠癌患者病理缓解的预测性生物标志物。
直肠癌患者的主要治疗为新辅助治疗(NT)后手术。免疫生物标志物正成为预测NT应答的潜在指标。本研究开展荟萃分析,评估其预测意义。
系统检索PubMed、Ovid MEDLINE和EMBASE数据库,以识别符合条件的研究。纳入接受NT的直肠癌患者研究,且至少一种关注的免疫标志物经免疫组化(IHC)在治疗前活检样本中评估其预测价值。
17项报告数据充分的研究符合荟萃分析纳入标准。总CD3⁺、CD4⁺和CD8⁺TIL(肿瘤浸润淋巴细胞)水平较高,以及基质和上皮内CD8⁺细胞区室水平较高,均显著预测NT后较好的病理学应答。此外,PD-L1总表达(包括肿瘤细胞和免疫细胞表达)水平较高也与较好的病理学应答相关。相反,上皮内CD4⁺ TIL水平较高与病理学应答较差相关。FoxP3⁺ TIL、肿瘤细胞PD-L1和CTLA-4均与治疗应答无相关性。
该荟萃分析表明,在接受直肠癌NT的患者中,高密度TIL可能是预测病理学应答的生物标志物。
The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta-analysis to estimate their predictive significance.
A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included.
Seventeen studies reporting sufficient data met the inclusion criteria for meta-analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD-L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD-L1 and CTLA-4 were not correlated to the treatment response.
This meta-analysis indicated that high-density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.
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