The prognostic value of the tertiary lymphoid structure in gastrointestinal cancers

Background: Numerous studies and research papers have provided evidence suggesting that tertiary lymphoid structures (TLS) play a crucial role in combating and suppressing tumor growth and progression. Despite the wealth of information on the significance of TLS in various types of cancer, their prognostic value in gastrointestinal (GI) cancers remains uncertain. Therefore, this meta-analysis investigated the prognostic value of TLS in GI cancers. Methods: We searched Web of science, Pubmed, Embase and Cochrane Library for studies that met the requirements as of May 1, 2023, and the hazard ratio (HR) and the corresponding 95% confidence interval (CI) were included in the analysis. The bioinformatics analysis results based on the TCGA database are used to supplement our research. Results: The meta-analysis included 32 studies involving 5778 patients. The results of comprehensive analysis showed that TLS-High is associated with prolonged OS (HR=0.525,95%CI:0.447-0.616 (P < 0.001), RFS (HR=0.546,95%CI:0.461-0.647, P < 0.001), DFS (HR=0.519,95%CI:0.417-0.646, P < 0.001) and PFS (HR=0.588,95%CI:0.406-0.852, P=0.005) in GI cancer. Among the patients who received immunotherapy, TLS-High is associated with significantly prolonged OS (HR=0.475, 95%CI:0.282-0.799, P=0.005) and PFS(HR=0.576, 95%CI:0.381-0.871, P=0.009). It is worth noting that subgroup analysis showed that there was no significant relationship between TLS and OS(HR=0.775, 95%CI:0.570-1.053,P=0.103) in CRC. And when Present is used as the cut-off criteria of TLS, there is no significant correlation between TLS and OS (HR=0.850, 95%CI:0.721-1.002, P=0.053)in HCC. Conclusion: TLS is a significant predictor of the prognosis of GI cancers and has the potential to become a prognostic biomarker of immunotherapy-related patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023443562.