CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:AI-driven spatial analysis of tumor-infiltrating lymphocytes predicts chemo-immunotherapy response in triple-negative breast cancer.
AI-driven spatial analysis of tumor-infiltrating lymphocytes predicts chemo-immunotherapy response in triple-negative breast cancer.
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本研究建立了一个 AI 驱动的 HE 分析流程,精确量化了肿瘤-免疫相互作用的空间决定因素。淋巴细胞的空间组织,特别是与肿瘤细胞的邻近性和淋巴细胞聚集模式,可作为化疗-免疫治疗反应的关键预测因子,其价值超越密度指标。经过验证的 MP 级预测模型展示了在 TNBC 管理临床决策中的转化潜力,尽管仍需在更大队列中进行外部验证。
三阴性乳腺癌(TNBC)是一种侵袭性亚型,由于缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)表达,治疗选择有限。虽然新辅助免疫治疗显示出前景,但三级淋巴结构(TLS)和TIL(肿瘤浸润淋巴细胞)(TILs)的空间组织对治疗效果的影响仍未完全明确。本探索性研究旨在建立基于AI的定量框架,用于分析肿瘤-免疫空间相互作用,并开发化疗-免疫治疗反应的预测模型。
我们开发了一个集成AI流程,用于自动分析苏木精-伊红(HE)染色的乳腺癌样本。该框架包括:1)TLS检测与分类,2)TIL定量,以及3)淋巴细胞与肿瘤细胞之间的空间关系映射。通过多变量统计学识别了与Miller-Payne(MP)反应分级相关的生物标志物,从而能够构建随机森林预后模型。
TLS识别模型与病理学家表现出高度一致性(=0.73),而TIL分类器达到了0.92的准确率。对32例接受新辅助化疗-免疫治疗的TNBC病例的HE图像分析揭示了显著关联:间质淋巴细胞密度和百分比与MP分级呈正相关(p<0.05);2细胞和3细胞淋巴细胞聚集体中的平均细胞计数未显示显著相关性;在10-30 m半径范围内,淋巴细胞与肿瘤细胞之间较短的平均最小距离与MP分级呈负相关(p<0.05)。基于空间特征的预测模型达到了0.81的AUC(95% CI:0.76-0.86)。
We developed an integrated AI pipeline for automated analysis of hematoxylin-eosin (HE)-stained breast cancer samples. The framework incorporates: 1) TLS detection and classification, 2) TIL quantification, and 3) spatial relationship mapping between lymphocytes and tumor cells. Biomarkers associated with Miller-Payne (MP) response grades were identified using multivariate statistics, enabling construction of a random forest prognostic model.
The TLS recognition model demonstrated substantial agreement with pathologists ( =0.73), while the TIL classifier achieved 0.92 accuracy. Analysis of 32 HE images from triple-negative breast cancer (TNBC) cases treated with neoadjuvant chemo-immunotherapy revealed significant associations: stromal lymphocyte density and percentage positively correlated with MP grades (p<0.05); average cell counts in 2-cell and 3-cell lymphocyte aggregates showed no significant correlations; shorter mean minimum distances between lymphocytes and tumor cells within 10-30 m radius range were inversely associated with MP grades (p<0.05). The spatial-feature-based prediction model achieved an AUC of 0.81 (95% CI: 0.76-0.86).
This study established an AI-driven HE analysis pipeline that precisely quantified spatial determinants of tumor-immune interactions. Lymphocyte spatial organization, particularly proximity to tumor cells and lymphocyte aggregation patterns, serves as a critical predictor of chemo-immunotherapy response beyond density metrics. The validated MP-grade prediction model demonstrates translational potential for clinical decision-making in TNBC management, although external validation in larger cohorts is warranted.
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