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Tertiary lymphoid structures show infiltration of effective tumor-resident T cells in gastric cancer.

ABSTRACT: Several studies have reported that tissue-resident memory T cells (TRM cells) or tertiary lymphoid structures (TLSs) are associated with a good prognosis. The aim of this study was to clarify the association of TRM cells and TLSs in the tumor immune microenvironment in gastric cancer (GC). We performed immunohistochemical and immunofluorescence staining to detect the presence of CD103⁺ T cells and to assess the association between CD103⁺ T cells and TLSs. CD103⁺ T cells were observed in the tumor epithelium accompanied by CD8⁺ T cells and were associated with a better prognosis in GC. Furthermore, CD103⁺ T cells were located around TLSs, and patients with CD103^high had more rich TLSs. Patients who had both CD103^high cells and who were TLS-rich had a better prognosis than patients with CD103^low cells and who were TLS-poor. Moreover, for patients who received PD-1 blockade therapy, CD103^high and TLS-rich predicted a good response. Flow cytometry was performed to confirm the characteristics of CD103⁺ CD8⁺ T cells and showed that CD103⁺ CD8⁺ T cells in GC expressed higher levels of PD-1, granzyme B, and interferon-γ than CD103^- CD8⁺ T cells. Our results suggested that CD103⁺ CD8⁺ cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC.

SUBMITTER: Mori T

PROVIDER: S-EPMC8088970 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma.

Project description:BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. However, the roles of TILs, TLS, and their correlation in Epstein-Barr Virus-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) are largely unknown.MethodsTo observe the correlation among TILs, TLS, and clinicopathological characteristics and their prognostic significance in EBVaGC and EBVnGC, respectively. TILs and TLS were assessed by morphology and/or immunohistochemistry, and accompanied by clinicopathological analysis from 846 gastric cancer patients in multiple institutions.ResultsForty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by in situ hybridization, respectively. For EBVnGC, higher TILs grade was correlated with TLS-present. EBVnGC patients with high TILs grade and TLS-present exhibited survival benefits. TILs (P = 0.001) and TLS (P = 0.003), especially TILs & TLS (P < 0.001) were independent prognostic factors in EBVnGC. A nomogram was constructed and validated for predicting the probability of overall survival and performed well with a good calibration. No significant prognostic value was detected in EBVaGC.ConclusionTILs and TLS, especially TILs & TLS were promising prognostic indicators for overall survival in EBVnGC. TILs and TLS were highly overlapping in their extent and prognostic abilities, and may be considered as a coindicator of prognosis of gastric cancer. The evaluations of TILs and TLS are simple and can be assessed routinely in pathological diagnosis.

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

Project description: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 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.ResultsThe TLS distribution was 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 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 (p = 0.007), peri-CD8+ (p = 0.019) and peri-GrB+TILs (p = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs (p = 0.019) and TLSs (p = 0.037) were independent prognostic predictor for GC patients.ConclusionsWe 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.

| S-EPMC10895974 | biostudies-literature

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