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

TL;DR - Conserved Immune Topology (CIT) augments pathology foundation-model embeddings with spatial immune descriptors to improve cross-cancer MSI-H prediction. It enables stronger zero-shot transfer across colorectal and stomach cancer cohorts without annotations or target-domain data.

• CIT captures tertiary lymphoid structures, peritumoral immune reactions, multi-scale tumor-infiltrating lymphocyte density, and immune-tumor mixing.
• Immune-associated image tiles are identified through unsupervised clustering of frozen foundation-model embeddings and spatial coordinates.
• On zero-shot cross-cancer transfer, CIT raised TransMIL AUC from 0.6627 to 0.7161, a 0.0534 absolute gain (p=0.003).
• Improvements held across all three tested multiple-instance learning aggregators despite scanner, site, and organ-specific distribution shifts.