[Research advances in the value of tertiary lymphoid structures for gastrointestinal tumors during the immunotherapy...

In the era of tumor immunotherapy, Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues in the tumor microenvironment, which are composed of B cell follicular regions and T cell regions, and their mature structures contain functional germinal centers. Currently, biomarkers such as PD-L1 expression, microsatellite instability (MSI)/mismatch repair deficiency (dMMR), and tumor mutational burden (TMB) are used to predict responses to immunotherapy in gastrointestinal tumors. However, their clinical utility is limited by insufficient sensitivity and narrow applicability across patient populations. The abundance, spatial distribution, maturity and cellular components of TLS are not only significantly related to the survival of patients, but also have important predictive value for the efficacy of immune checkpoint inhibitors (ICI), offering the potential to overcome the limitations of existing biomarkers. Furthermore, integrating TLS with multi-omics data could enable the construction of more accurate prognostic and predictive models, thereby enhancing their clinical applicability. Meanwhile, inducing TLS formation has emerged as a novel immunotherapeutic strategy. In this review, we systematically summarize recent advances in TLS research in gastrointestinal tumors and discuss its potential applications in prognostic assessment, prediction of immunotherapy efficacy, and clinical translation, thereby providing new directions for optimizing personalized immunotherapy.