ArticleFrontiers in immunology2026
Macroscopic fractal dynamics characterize the "physical-metabolic" dual barriers and systemic immune exhaustion associated with primary resistance to immunotherapy in liver metastases.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Liver metastases are associated with systemic immune tolerance and primary resistance to immune checkpoint inhibitors (ICIs) by establishing complex physical and metabolic barriers within the tumor immune microenvironment (TIME). We developed a non-invasive macroscopic fractal dynamics framework to map these microenvironmental barriers across scales, aiming to predict ICI efficacy in colorectal cancer liver metastases (CRLM) and lung squamous cell carcinoma (SCC). Methods: This single-center, retrospective, proof-of-concept cohort study consecutively enrolled 472 patients with CRLM or SCC liver metastases. Patients were divided into a training cohort (n=400, 2019-2024) and an independent validation cohort (n=72, 2025). Vascular fractal acceleration ( Results: CRLM and SCC displayed distinct fractal trajectories indicative of metabolic and physical barriers, respectively. High Conclusions: Macroscopic fractal dynamics offer a non-invasive, cross-scale method to evaluate the "physical-metabolic" dual microenvironmental barriers in liver metastases. The combined IRJS and dynamic Δ
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