Conserved Immune Topology Improves Pathology Foundation Model Generalization for Cross-Cancer MSI-H Prediction

The paper introduces Conserved Immune Topology (CIT), a lightweight spatial representation that enhances cross‑cancer MSI‑H prediction by augmenting pathology foundation‑model embeddings with immune‑related descriptors. CIT identifies immune‑associated tiles via unsupervised clustering and encodes features such as tertiary lymphoid structures, peritumoral immune reactions, tumor‑infiltrating lymphocyte density, and immune‑tumor mixing, all without requiring annotations or target‑domain data. In cross‑site and cross‑cancer experiments on CPTAC‑COAD and TCGA‑STAD cohorts, CIT improved zero‑shot TransMIL AUC from 0.6627 to 0.7161, demonstrating that spatial immune topology can provide an organ‑invariant representation for MSI‑H prediction.

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