CELL INTELLIGENCE · 肿瘤细胞治疗研究

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基于组织病理学切片的 AI 驱动免疫分析用于直肠癌放化疗结局预测：一项使用临床试验和真实世界队列的研究

英文原题：AI-powered immune profiling from histopathology slides for chemo-radiotherapy outcome prediction in rectal cancer: a study using clinical trial and real-world cohorts.

查看英文原题

AI-powered immune profiling from histopathology slides for chemo-radiotherapy outcome prediction in rectal cancer: a study using clinical trial and real-world cohorts.

PubMed 2025/11/17（内容时间） EBioMedicine Q1 · IF 11.2（JCR 2025）

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结直肠癌地区：欧洲
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研究概要

这些发现提示，AI 驱动的免疫分析在接受 nCRT 的 LARC 患者临床决策中具有潜在应用价值。

研究思路结论见上方概要

背景

肿瘤免疫微环境对局部晚期直肠癌（LARC）预后的影响尚不明确。本研究定量评估TIL（肿瘤浸润淋巴细胞）（TILs）、肿瘤相关巨噬细胞（TAMs）、有丝分裂活性及DNA突变在接受新辅助放化疗（nCRT）的LARC患者预后预测中的协同影响。

方法

三个队列（ARISTOTLE-RC、UCLH-RC、TCGA-CRC）根据AI量化的TIL、TAM和核分裂象密度进行分层，临界值在留出子集上确定，并与DNA突变整合，以评估与无病生存期（DFS）和总生存期（OS）的相关性。还评估了CRT前后的免疫细胞动态变化。

结果

在ARISTOTLE-RC中，TIL+患者的DFS（HR = 0.59，95% CI：0.39-0.90，p = 0.013）和OS（HR = 0.42，95% CI：0.24-0.73，p < 0.005）显著改善，而TAM+与较短的DFS相关（HR = 1.65，95% CI：1.00-2.72，p = 0.045）。在UCLH-RC和TCGA-CRC中观察到相似的模式。TIL+/KRAS-患者的DFS（HR = 0.41，95% CI：0.22-0.75，p < 0.005）和OS（HR = 0.28，95% CI：0.13-0.62，p < 0.005）显著改善。在TP53突变患者中，TAM+组显示较短的DFS（HR = 1.46，95% CI：1.07-2.01，p = 0.0151），而在TP53野生型患者中，两个亚组之间未观察到DFS差异（HR = 1.00，95% CI：0.66-1.52，p = 0.9930）。在nCRT后从TIL-转变为TIL+的患者DFS改善（HR = 0.70，95% CI：0.50-0.97，p = 0.028），并表现出显著更高的治疗前有丝分裂指数（平均差 = 9.36，95% CI：1.87-16.85，p = 0.0385）。

展开英文摘要原文
BACKGROUND

The impact of the tumour-immune microenvironment on locally advanced rectal cancer (LARC) outcomes remains unclear. This study quantitatively assesses the synergistic influence of tumour-infiltrating lymphocytes (TILs), tumour-associated macrophages (TAMs), mitotic activity, and DNA mutations in predicting outcomes for LARC patients undergoing neoadjuvant chemo-radiotherapy (nCRT).

METHODS

Three cohorts (ARISTOTLE-RC, UCLH-RC, TCGA-CRC) were stratified by densities of AI-quantified TILs, TAMs, and mitotic figures with cut-offs identified on a hold-out subset and integrated with DNA mutations to assess correlations with disease-free survival (DFS) and overall survival (OS). Immune cell dynamics pre- and post-CRT were also evaluated.

FINDINGS

In ARISTOTLE-RC, TIL + patients had significantly improved DFS (HR = 0.59, 95% CI: 0.39-0.90, p = 0.013) and OS (HR = 0.42, 95% CI: 0.24-0.73, p < 0.005), while TAM + was associated with shorter DFS (HR = 1.65, 95% CI: 1.00-2.72, p = 0.045). Similar patterns were observed in UCLH-RC and TCGA-CRC. TIL + /KRAS - patients had significantly improved DFS (HR = 0.41, 95% CI: 0.22-0.75, p < 0.005) and OS (HR = 0.28, 95% CI: 0.13-0.62, p < 0.005). In TP53-mutated patients, TAM + group showed shorter DFS (HR = 1.46, 95% CI: 1.07-2.01, p = 0.0151), while among TP53-wild-type patients, no difference in DFS (HR = 1.00, 95% CI: 0.66-1.52, p = 0.9930) was observed between the two subgroups. Patients who transitioned after nCRT from TIL - to TIL + had improved DFS (HR = 0.70, 95% CI: 0.50-0.97, p = 0.028) and exhibited a significantly higher pre-treatment mitotic index (mean difference = 9.36, 95% CI: 1.87-16.85, p = 0.0385). INTERPRETATION: These findings suggest the potential utility of AI-driven immune profiling for clinical decision-making in LARC patients undergoing nCRT. FUNDING: Cancer Research UK (RRNPSF-Jan21/100001, A18745, C7893/A2899), UK Research and Innovation (MR/T040785/1).

论文信息

作者
Shen Z、Brand D、Simard M、Levine AP、Hindocha S、Mistry T、Oukrif D、Lopes A
单位
Department of Medical Physics and Biomedical Engineering, University College London, London, UK. Electronic address: zhuoyan.shen.18@ucl.ac.uk.United Kingdom
期刊
EBioMedicine2025 Dec
原文标识
PubMed 41253645　·　DOI 10.1016/j.ebiom.2025.105993

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