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

arXiv: https://arxiv.org/abs/2609.05182 · HTML: https://mlsanity.com/paper/2609.05182/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 34 references that are in the map.
- First posted on arXiv 4 Sep 2026.

## Builds on (most cited first, 7 of 7)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [DeepSMILE: Contrastive self-supervised pre-training benefits MSI and HRD classification directly from H&E whole-slide images in colorectal and breast cancer](https://mlsanity.com/paper/2107.09405/) (2021)
- [Transfer Learning from One Cancer to Another via Deep Learning Domain Adaptation](https://mlsanity.com/paper/2601.14678/) (2026)

## Abstract (arXiv)

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.