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<p>Endoplasmic reticulum stress-related cancer-associated fibroblasts (ERS–CAF) remodel the tumor microenvironment and drive immune exclusion and therapy resistance in chordoma, yet routine and non-invasive readouts of this biology are lacking. We hypothesized that standard pre-operative MRI and H&amp;E whole-slide images (WSI) encode image-based surrogates of ERS–CAF-driven immunoregulation that can be learned and generalized across cancers. Three bulk-transcriptomic reference scores were defined for surrogate supervision, capturing ERS-program activity, ERS–CAF-immuneligand-receptor crosstalk and microenvironmental heterogeneity. In 126 chordoma cases, a stage-wise multimodal framework integrating calibrated WSI attention, gated radiopathomic fusion and domain alignment showed strong concordance with molecular profiles, independent prognostic value and biologically specific localization to fibrotic immune-excluded regions. These associations were generalized in zero-shot analyses to the TCGA pan-cancer. An MRI-only distilled model preserved most predictive performance with substantial gains in efficiency, supporting scalable non-invasive clinical application.</p>

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Decoding the ERS–CAF immunoregulatory axis via multimodal AI and its pan-cancer prognostic and therapeutic predictive value

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • Bo-Wen Zheng,
  • Chao Xia,
  • Ming Tang,
  • Wei Huang,
  • Bo-Yv Zheng,
  • Hua-Qing Niu,
  • Jing Li,
  • Tao-Lan Zhang,
  • Hong Zhou,
  • Ming-Xiang Zou

摘要

Endoplasmic reticulum stress-related cancer-associated fibroblasts (ERS–CAF) remodel the tumor microenvironment and drive immune exclusion and therapy resistance in chordoma, yet routine and non-invasive readouts of this biology are lacking. We hypothesized that standard pre-operative MRI and H&E whole-slide images (WSI) encode image-based surrogates of ERS–CAF-driven immunoregulation that can be learned and generalized across cancers. Three bulk-transcriptomic reference scores were defined for surrogate supervision, capturing ERS-program activity, ERS–CAF-immuneligand-receptor crosstalk and microenvironmental heterogeneity. In 126 chordoma cases, a stage-wise multimodal framework integrating calibrated WSI attention, gated radiopathomic fusion and domain alignment showed strong concordance with molecular profiles, independent prognostic value and biologically specific localization to fibrotic immune-excluded regions. These associations were generalized in zero-shot analyses to the TCGA pan-cancer. An MRI-only distilled model preserved most predictive performance with substantial gains in efficiency, supporting scalable non-invasive clinical application.