Yan Leyfman, Medical Oncologist, Co-Founder and Executive Director of MedNews Week, shared a post on LinkedIn:
“For years, tertiary lymphoid structures (TLSs) have been viewed as one of cancer immunology’s most intriguing mysteries.
These immune cell “mini-lymph nodes” can form inside tumors, and their presence is often associated with better outcomes. But not all TLSs are created equal.
In a remarkable pan-cancer study spanning 12 tumor types, researchers built a comprehensive atlas of TLS biology using spatial transcriptomics and AI-powered pathology.
What emerged was a much more nuanced picture.
TLSs exist along a maturation spectrum—from early immune aggregates to highly organized, germinal center-like structures—and their location within the tumor matters. The most mature TLSs were associated with coordinated B-cell and T-cell activation, antigen presentation, interferon signaling, and other hallmarks of effective antitumor immunity.
Perhaps most fascinating, the influence of TLSs appeared to extend beyond the structures themselves.
Tumor regions closest to intratumoral TLSs displayed stronger immune activation programs, while areas farther away were enriched for proliferation, MYC signaling, cell-cycle activity, and invasive pathways. In other words, TLSs may create local immune ecosystems that shape tumor behavior in a distance-dependent manner.
To bring these insights into clinical practice, investigators trained an AI model capable of identifying TLSs and predicting their maturation state directly from routine H&E pathology slides. They then developed a maturation-aware TLS score that outperformed conventional TLS measurements in predicting survival and treatment outcomes across multiple cancers.
The message is clear: the question is no longer whether a tumor contains TLSs.
The more important question may be which TLSs are present, how mature they are, and where they are located.
This work moves TLSs from a simple biomarker toward a spatially informed framework for understanding—and potentially predicting—antitumor immunity.”
Title: Pan-cancer spatial atlas of tertiary lymphoid structures
Authors: 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.
Read the article here.
Other articles about Tertiary Lymphoid Structures on OncoDaily.