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Immunotherapy and Immune Responses / Immune Cells in Cancer · Journal article
Molecular Biomedicine · September 4, 2026
A consensus or society position rather than new primary data.
This is a narrative review synthesizing evidence that mature tertiary lymphoid structures with intact germinal centers act as independent favorable prognostic biomarkers and predict superior responses to immune checkpoint inhibitors across solid cancers. The review consolidates current understanding of TLS development, detection methods, and therapeutic strategies, but does not report new primary clinical or experimental data.
Journal article. Patients across solid cancers with tertiary lymphoid structures.
Mature TLS with intact germinal centers serve as independent favorable prognostic biomarkers Mature TLS predict superior responses to immune checkpoint inhibitors TLS heterogeneity in maturity, spatial localization, and cellular composition results in dual pro-tumor and anti-tumor functions
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
Clinicians should recognize TLS maturity and germinal center status as prognostic indicators and potential predictors of immunotherapy response. However, the lack of standardized detection methods and definitions limits immediate clinical implementation until consensus assessment criteria are established.
A comprehensive narrative review synthesizing current understanding of tertiary lymphoid structures in cancer, their prognostic value, and therapeutic strategies, without reporting new primary data or clinical trials.
Clinicians should recognize TLS maturity and germinal center status as prognostic indicators and potential predictors of immunotherapy response. However, the lack of standardized detection methods and definitions limits immediate clinical implementation until consensus assessment criteria are established.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates formed under chronic inflammatory tumor microenvironments. Clinical cohorts across solid cancers demonstrate that mature TLS with intact germinal centers serve as independent favorable prognostic biomarkers and predict superior responses to immune checkpoint inhibitors. However, the differences in maturity, spatial localization and cellular composition of TLSs result in heterogeneity in their immunostimulation or immunosuppression, thereby exhibiting dual functions of promoting or anti-tumor. Furthermore, there are significant differences in the maturity assessment methods and definitions of TLS, which jointly hinder the clinical evaluation and targeted treatment of TLSs. In this review, we integrate current understanding of TLS development, molecular drivers, and stromal licensing, and dissect the key mechanisms by which TLS contribute to anti-tumor immunity within tumors. We consolidate standardized TLS detection methods encompassing pathology, multi-omics, and radiogenomics, and further explore the translational value of TLS maturation status, germinal center-like responses, and intratumoral versus peritumoral localization in prognosis and immune checkpoint blockade. We systematically elaborate therapeutic strategies for inducing functional TLS, dissect the intrinsic mechanisms by which TLS synergistically boost the efficacy of adoptive cell therapy and tumor vaccines, and outline major bottlenecks hindering clinical translation. Collectively, this work constructs a comprehensive multi-dimensional framework for TLS research and provides actionable insights to develop TLS-targeted immunotherapies for human cancers.
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