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:Artificial intelligence-powered H&E-based quantification of spatial tumor-infiltrating lymphocyte distribution identifies prognostic immune niches in colorectal cancer.
Artificial intelligence-powered H&E-based quantification of spatial tumor-infiltrating lymphocyte distribution identifies prognostic immune niches in colorectal cancer.
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AI 驱动的 TILs 空间分析,尤其是 TSB 评分,展现出与传统 Immunoscore 相当的预后性能,从而支持了空间免疫分析和 AI 驱动的 H&E 染色切片分析在改善 CRC 风险分层中的价值。
TIL(肿瘤浸润淋巴细胞)(TILs)在结直肠癌(CRC)中的预后意义已得到充分确立;然而,现有方法无法充分捕捉其空间分布。我们采用基于人工智能(AI)的方法,研究了CRC中TILs空间分布的预后意义。
共纳入202例II-III期CRC患者。采用基于AI的苏木精-伊红(H&E)染色图像分析,对肿瘤内(iTIL)和间质(sTIL)区域的TIL密度进行量化。根据与肿瘤-间质边界(TSB)的邻近程度,将TIL进一步分为核心iTIL、边界iTIL、边界sTIL和最外层sTIL。Immunoscore根据肿瘤中心和浸润边缘的CD3 + 和CD8 + T细胞密度计算。
基于AI的评估与病理学家评估之间的相关性(iTIL:r = 0.57;sTIL:r = 0.70)与病理学家之间的相关性(iTIL:r = 0.47;sTIL:r = 0.70)相当。在单因素Cox回归分析中,边界区iTIL、边界区sTIL和最外层sTIL与无复发生存期(RFS)显著相关,而核心区iTIL则无显著相关性。通过纳入具有预后显著意义的区域,构建了复合TIL评分和TSB评分。在多因素分析中,TIL评分(p = 0.001)、TSB评分(p < 0.001)和Immunoscore(p < 0.001)均可独立预测RFS。在微卫星高度不稳定肿瘤中,仅TSB评分仍具有预后显著意义。
The prognostic significance of tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) is well established; however, existing approaches inadequately capture their spatial distribution. We investigated the prognostic implications of TIL spatial distribution in CRC using an artificial intelligence (AI)-based method.
A total of 202 patients with stage II-III CRC were included. TIL densities in intratumoral (iTIL) and stromal (sTIL) regions were quantified using AI-based analysis of hematoxylin and eosin (H&E)-stained images. Based on proximity to the tumor-stromal border (TSB), TILs were subclassified into core iTIL, bounding iTIL, bounding sTIL, and outermost sTIL. Immunoscore was calculated from CD3 + and CD8 + T-cell densities in the tumor center and invasive margin.
Correlations between AI-based and pathologist assessments (iTIL: r = 0.57; sTIL: r = 0.70) were comparable to inter-pathologist correlations (iTIL: r = 0.47; sTIL: r = 0.70). In univariate Cox regression analysis, bounding iTIL, bounding sTIL, and outermost sTIL were significantly associated with recurrence-free survival (RFS), whereas core iTIL was not. Composite TIL and TSB scores were developed by incorporating the prognostically significant regions. In multivariable analysis, the TIL score (p = 0.001), TSB score (p < 0.001), and Immunoscore (p < 0.001) independently predicted RFS. In microsatellite instability-high tumors, only the TSB score remained prognostically significant.
AI-powered spatial analysis of TILs, particularly the TSB score, demonstrated prognostic performance comparable to conventional Immunoscore, thereby supporting the value of spatial immune profiling and AI-driven analysis of H&E-stained slides for improved risk stratification in CRC.
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