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Updated: May 31, 2026
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Three-Dimensional Imaging of Tumor-Bearing Tissue Using the Iterative Bleaching Extends Multiplexity Approach
Published on: April 25, 2025
Pan-cancer spatial atlas of tertiary lymphoid structures
Kyung Serk Cho1, Yunhe Liu1, Guangsheng Pei1
1Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Science (New York, N.Y.)
|May 28, 2026
Summary
Tertiary lymphoid structures (TLSs) are key to antitumor immunity. This study maps TLS organization and maturation across cancers, revealing a new AI-driven score to predict patient outcomes.
Area of Science:
- Immunology
- Oncology
- Computational Biology
Background:
- Tertiary lymphoid structures (TLSs) play a crucial role in antitumor immune responses.
- The spatial organization, maturation, and clinical significance of TLSs in various cancers are not fully understood.
Purpose of the Study:
- To create a pan-cancer atlas of TLSs using spatial transcriptomics.
- To characterize TLS spatial architecture and maturation states.
- To develop a scalable method for assessing TLS maturation and its clinical relevance.
Main Methods:
- Analysis of spatial transcriptomics data from 12 cancer types.
- Ultrahigh-plex single-cell spatial profiling to study niche cell populations and tumor programs.
- Training an artificial intelligence (AI) framework to predict TLS maturation from H&E images.
- Validation of the AI framework and a novel composite score across TCGA and independent cohorts.
Main Results:
- Construction of a pan-cancer TLS atlas, detailing spatial architecture and maturation states.
- Identification of coordinated niche cell remodeling and distance-dependent tumor program gradients during TLS maturation.
- Development and validation of an AI tool for predicting TLS maturation from histology.
- A novel maturation-aware composite score robustly stratifies patients across cancer types and treatment settings, outperforming existing metrics.
Conclusions:
- TLS maturation is a complex process involving specific cellular niches and tumor microenvironment interactions.
- An AI-powered approach enables scalable and accurate assessment of TLS maturation from standard histology.
- The developed composite score offers a powerful, clinically relevant tool for predicting patient stratification and outcomes in cancer immunotherapy.
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