Multi-omics of tertiary lymphoid structures in breast cancer: clinical significance and biomarker potential
- 1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Abstract
Background: Tertiary lymphoid structures (TLSs) are organized immune aggregates that can support local adaptive immune responses within the tumor microenvironment. In breast cancer, particularly triple-negative breast cancer (TNBC), the presence and maturation of TLSs have been associated with prognosis and treatment response; however, heterogeneity in TLS definition, maturation criteria, spatial sampling, and analytical platforms currently limits standardization and routine clinical implementation.
Main body: Conventional histopathology provides structural information but limited molecular resolution, whereas single-cell RNA sequencing loses the spatial context that is central to TLS organization. High-resolution spatial and multi-omics technologies can partly bridge these gaps by characterizing TLS cellular composition, molecular interactions, and tissue architecture in situ . This review summarizes the biological features, histopathological classification, multi-omics characterization, clinical associations, and emerging therapeutic strategies related to TLSs in breast cancer, with particular attention to methodological limitations and translational barriers.
Conclusion: More precise characterization of TLSs may inform future biomarker development and therapeutic strategies in breast cancer. Prospective validation, standardized assessment, and demonstration of incremental clinical utility are required before TLS-based approaches can be incorporated into routine clinical decision-making.
Related
- From density to spatial function: spatial multi-omics, composite biomarker design, and therapeutic engineering of tertiary lymphoid structures in solid tumors
- Prognostic and Spatial Organization of Tertiary Lymphoid Structures in Pancreatic Ductal Adenocarcinoma
- Temporal and therapeutic confounders in predicting efficacy of immunotherapy rechallenge via baseline intratumoral tertiary lymphoid structures.
- Co-targeting KRAS and BCL-2 induces pyroptosis and antitumor tertiary lymphoid structures
- Neutrophil-epithelial niches arrest B-cell maturation in dysfunctional tertiary lymphoid structures of gastric cancer neoadjuvant immunochemotherapy.
BibTeX
@article{chen2026multiomics,
title = {{Multi-omics of tertiary lymphoid structures in breast cancer: clinical significance and biomarker potential}},
author = {Chang’e Chen and Haiping Song},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1892848},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892848/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-omics of tertiary lymphoid structures in breast cancer: clinical significance and biomarker potential
AU - Chang’e Chen
AU - Haiping Song
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1892848
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892848/full
AB - Background: Tertiary lymphoid structures (TLSs) are organized immune aggregates that can support local adaptive immune responses within the tumor microenvironment. In breast cancer, particularly triple-negative breast cancer (TNBC), the presence and maturation of TLSs have been associated with prognosis and treatment response; however, heterogeneity in TLS definition, maturation criteria, spatial sampling, and analytical platforms currently limits standardization and routine clinical implementation. Main body: Conventional histopathology provides structural information but limited molecular resolution, whereas single-cell RNA sequencing loses the spatial context that is central to TLS organization. High-resolution spatial and multi-omics technologies can partly bridge these gaps by characterizing TLS cellular composition, molecular interactions, and tissue architecture in situ . This review summarizes the biological features, histopathological classification, multi-omics characterization, clinical associations, and emerging therapeutic strategies related to TLSs in breast cancer, with particular attention to methodological limitations and translational barriers. Conclusion: More precise characterization of TLSs may inform future biomarker development and therapeutic strategies in breast cancer. Prospective validation, standardized assessment, and demonstration of incremental clinical utility are required before TLS-based approaches can be incorporated into routine clinical decision-making.
SN - 1664-3224
ER -