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:Prognostic Significance of Immune and Stromal Components in Colorectal Cancer.
Prognostic Significance of Immune and Stromal Components in Colorectal Cancer.
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结直肠癌(CRC)肿瘤微环境包括癌相关成纤维细胞和多种免疫细胞;这些成分的预后意义日益受到重视。
采用适用于常规病理实践的方法评估 CRC 肿瘤微环境。设计:对 930 例 CRC 的全部苏木精-伊红(H&E)切片进行全面复核,评估局部免疫应答和肿瘤-间质比(TSR)。局部免疫应答通过肿瘤周围炎性浸润[Klintrup-Mäkinen 及改良 Klintrup-Mäkinen 方法]、肿瘤内间质 TIL[国际 TIL 工作组系统和深部间质 TIL 系统]以及克罗恩样淋巴反应(CLR)进行评估。
多变量分析显示,年龄(>68 岁)、III–IV 期、微卫星稳定、印戒细胞癌/未分化癌、壁外静脉侵犯、高 TSR(>50%)和 CLR 是疾病特异性生存的独立预后因素。除微卫星稳定外,上述因素对无进展生存期也具有显著预后意义。在评估局部免疫应答的 4 种方法中,测量肿瘤内部最深层间质中的 TIL 比例,是无进展生存期的独立预测因子。
研究者认为,在 H&E 染色切片上评估 CLR、TSR 和间质 TIL,是一种实用、简便且具有显著预后价值的方法。
CONTEXT. —: In colorectal cancer (CRC), the tumor microenvironment includes cancer-associated fibroblasts and a variety of immune cells, which are increasingly recognized for their prognostic significance. OBJECTIVE. —: To evaluate the tumor microenvironment in CRC using methodologies applicable in routine pathologic practice. DESIGN. —: A comprehensive evaluation of the local immune response and tumor to stroma ratio (TSR) was performed in 930 CRC cases by thoroughly reviewing the whole hematoxylin-eosin (H&E) slides. Local immune responses were assessed using peritumoral inflammatory infiltration (Klintrup-M kinen and modified Klintrup-M kinen methods), intratumoral stromal tumor-infiltrating lymphocytes (TILs; International TILs Working Group system and deep stromal TIL system), and Crohn-like lymphoid reaction (CLR).
RESULTS. —: In the multivariate analysis, age (>68 years), stage III-IV, microsatellite stability, signet ring cell/undifferentiated carcinoma, extramural venous invasion, high TSR (>50%), and CLR were independent prognostic factors for disease-specific survival. Excluding microsatellite stability, these factors also served as significant prognostic indicators for progression-free survival.
Among the 4 methods for measuring local immune response, evaluating the proportion of TILs within the deepest intratumoral stroma was an independent predictor of progression-free survival. CONCLUSIONS. —: We suggest that evaluating CLR, TSR, and stromal TILs on hematoxylin-eosin-stained slides represents a practical and straightforward approach with significant prognostic value.
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