Author Identifier (ORCID)
Lidia B. Medhin: https://orcid.org/0000-0002-2438-5588
Lydia Warburton: https://orcid.org/0000-0001-9417-1596
Leslie Calapre: https://orcid.org/0000-0001-7595-6523
Elin S. Gray: https://orcid.org/0000-0002-8613-3570
Abstract
Background: Immune checkpoint inhibitors (ICIs) have improved outcomes across several cancers, yet many patients do not respond, highlighting the need for robust predictive biomarkers. Tertiary lymphoid structures (TLS), ectopic lymphoid aggregates that support local antigen presentation and adaptive immune activation, have emerged as potential indicators of favourable prognosis and immunotherapy responsiveness. Methods: This review summarises current clinical and translational evidence examining the prognostic and predictive value of TLS in solid malignancies. Studies assessing TLS presence, organisation, and biological function were identified through searches of major scientific databases and evaluated with respect to their association with patient outcomes and responses to ICIs. Results: Across multiple tumour types, TLS correlate with improved survival and enhanced anti‑tumour immune activity. TLS‑rich tumours typically show increased infiltration of effector immune cells and more inflamed tumour microenvironments. Several studies also indicate that TLS maturity, particularly the presence of germinal‑centre‑like features, strengthens their predictive value for ICI benefit. However, substantial variation exists in TLS assessment methods and definitions, limiting comparability and hindering translation into routine clinical use. Conclusions: TLS represent a promising biomarker for prognosis and immunotherapy response. Standardised evaluation methods and prospective clinical validation are essential to enable their integration into personalised treatment strategies.
Keywords
Biomarker, immunotherapy, tertiary lymphoid structures
Document Type
Journal Article
Date of Publication
3-1-2026
Volume
15
Issue
3
PubMed ID
41845556
Publication Title
Cancer Medicine
Publisher
Wiley
School
Centre for Precision Health / School of Medical and Health Sciences
Funders
Raine Medical Research Foundation
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Medhin, L. B., Amanuel, R., Warburton, L., Calapre, L., Amanuel, B., & Gray, E. S. (2026). The emerging role of tertiary lymphoid structures as predictive and prognostic biomarkers of immunotherapy in cancer. Cancer Medicine, 15(3), e71728. https://doi.org/10.1002/cam4.71728