The relationship of the tertiary lymphoid structures with the tumor-infiltrating lymphocytes and its prognostic value in gastric cancer

Abstract

IntroductionTo 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 methodsThe TLSs and four subtypes of TILs were assessed by immunohistochemistry (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 a valid TLSs.The number of labeled TILs were observed in 5 fields of the most positive cells in tumor center, invasive edge and within the TLSs, respectively, at a field of vision×40.ResultsThe TLSs distributed significantly higher in the tumor invasive edge than the tumor center (P <0.001). Similarly, the infiltrating density of CD8+T cells and GrB+T cells were highly distributed in the tumor infiltrating edge than the tumor center. While the total number of TILs and the FOXP3+T cells were on the contrary. There was a positive correlation between the density of TLSs and TILs either in the location or the immune phenotype. And a higher frequency of TILs and TLSs often associated with the favorable clinicopathologic parameters. Multivariate analysis revealed that the density of TILs (P= 0.019) and TLSs (P= 0.037) were the independent prognostic predictor for GC patients.ConclusionsThe formation of TLSs predicts an advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients and as a marker of efficient immunotherapies.