通过免疫空间结构增强模型,提升跨癌种微卫星不稳定性预测能力
Conserved Immune Topology Improves Pathology Foundation Model Generalization for Cross-Cancer MSI-H Prediction

- 基于无监督聚类提取免疫相关图像块,编码多种免疫空间特征
- 零样本跨癌种迁移使AUC提升0.0534(从0.6627到0.7161)
- 无需标注数据,适用于不同扫描仪和组织结构的跨癌种场景
病理基础模型结合多实例学习在单癌种队列中表现良好,但因器官特异性组织结构差异,跨癌种泛化仍存挑战。本文提出一致免疫拓扑(CIT),一种轻量级空间表征方法,用于跨癌种MSI-H预测。CIT通过无监督聚类识别免疫相关图像块,从冻结的基础模型嵌入和瓦片坐标中编码三级淋巴结构、瘤周免疫反应、多尺度肿瘤浸润淋巴细胞密度及免疫-肿瘤混合程度,无需标注或目标域数据。在包含扫描仪差异、分布偏移和器官特异性结构变异的CPTAC-COAD与TCGA-STAD队列上评估,采用CIT进行零样本跨癌种迁移后,TransMIL AUC由0.6627提升至0.7161,绝对提升0.0534(p=0.003),且所有三种MIL聚合器均实现一致改进。结果表明,空间免疫拓扑可能提供一种器官无关的表征,支持病理基础模型的跨癌种泛化。
原文摘要 · Abstract (English)
Pathology foundation models integrated with multiple instance learning achieve competitive accuracy within single-cancer cohorts, yet cross-cancer generalization remains unresolved due to organ-specific histological and architectural differences. In this paper, we propose Conserved Immune Topology (CIT), a lightweight spatial representation for cross-cancer MSI-H prediction that augments foundation-model embeddings with biologically motivated immune descriptors. CIT uses unsupervised clustering to identify immune-associated tiles, then encodes tertiary lymphoid structures, peritumoral immune reactions, multi-scale tumor-infiltrating lymphocyte density, and immune-tumor mixing from frozen foundation-model embeddings and tile coordinates without requiring annotations or target-domain data. The proposed method was evaluated under cross-site and cross-cancer settings using CPTAC-COAD and TCGA-STAD cohorts, which introduce scanner variability, distribution shifts, and organ-specific architectural variations. Zero-shot cross-cancer transfer with CIT increased TransMIL AUC from 0.6627 to 0.7161, an absolute gain of 0.0534 (p=0.003), with consistent improvements across all three MIL aggregators. These results suggest that spatial immune topology provides potentially an organ-invariant representation for MSI-H prediction, supporting cross-cancer generalization of pathology foundation models.
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