The Relationship of the Tertiary Lymphoid Structures with the Tumor-infiltrating Lymphocytes and Its Prognostic Value in Gastric Cancer

Introduction: To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC).

Material And Methods: The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40.

Results: The TLS distribution was significantly higher in the tumor invasive edge than the tumor center ( < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs ( = 0.007), peri-CD8+ ( = 0.019) and peri-GrB+TILs ( = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs ( = 0.019) and TLSs ( = 0.037) were independent prognostic predictor for GC patients.

Conclusions: We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.