2026年5月28日，德克萨斯大学
研究团队分析了12种癌症类型的空间转录组学，构建了泛癌症TLS图谱，并表征了TLS的空间结构和成熟状态。TLS成熟伴随着不同生态位细胞群的协调重塑和肿瘤程序中的距离依赖梯度，并由超高分辨率单细胞空间谱正交支持。为了实现可扩展的TLS分析，研究团队训练了一个人工智能框架，该框架直接从苏木精和伊红染色图像中预测TLS成熟状态，并在TCGA和独立治疗队列中对其进行评估。该课题组进一步推导了一个成熟感知的复合评分，捕获肿瘤内TLS状态组成，该评分将患者根据癌症和治疗情况进行分层，优于传统的TLS指标。
据了解，三级淋巴样结构（TLSs）是抗肿瘤免疫的关键调节因子，但其空间组织、成熟度和临床相关性在各种癌症中仍未完全确定。
附：英文原文
Title: Pan-cancer spatial atlas of tertiary lymphoid structures
Author: Kyung Serk Cho, Yunhe Liu, Guangsheng Pei, Jianfeng Chen, Yibo Dai, Yang Liu, Tieling Zhou, Antoine Bougouin, Alejandra Serrano, Khalida Wani, Akshaya Jadhav, Jimin Min, Sharia Hernandez, Wei Lu, Daiwei Zhang, Jiahui Jiang, Diana Shamsutdinova, Enyu Dai, Fuduan Peng, Ansam Sinjab, Paola A Guerrero, Idania Carolina Lubo Julio, Kai Yu, Helen Clark, Dipen Maru, Mingyao Li, Andrew Futreal, Sanghoon Lee, Luisa Maren Solis Soto, Lulu Shang, Pavlos Msaouel, Jaffer A. Ajani, Hannah Beird, Amir A. Jazaeri, Alexander J. Lazar, Catherine Sautes-Fridman, Wolf H. Fridman, Anirban Maitra, Humam Kadara, Jianjun Gao, Padmanee Sharma, Linghua Wang
Issue&Volume: 2026-05-28
Abstract: Tertiary lymphoid structures (TLSs) are critical regulators of antitumor immunity, yet their spatial organization, maturation, and clinical relevance remain incompletely defined across cancers. We analyzed spatial transcriptomics spanning 12 cancer types to construct a pan-cancer TLS atlas and characterized TLS spatial architecture and maturation states. TLS maturation was accompanied by coordinated remodeling of distinct niche cell populations and distance-dependent gradients in tumor programs, orthogonally supported by ultrahigh-plex single-cell spatial profiling. To enable scalable TLS profiling, we trained an artificial intelligence framework that predicts TLS maturation states directly from hematoxylin and eosin–stained images and evaluated it across TCGA and independent therapy cohorts. We further derived a maturation-aware composite score capturing intratumoral TLS state composition, which robustly stratifies patients across cancer and treatment contexts, outperforming conventional TLS metrics.
DOI: adz2742
Source: https://www.science.org/doi/10.1126/science.adz2742