[Research on the evaluation of the efficacy of immunotherapy for gastric cancer by tertiary lymphoid structures].

Objective: To investigate the prognostic and predictive value of tertiary lymphoid structures (TLS) in gastric cancer patients undergoing immunotherapy. Methods: Clinical and pathological data, along with tumor tissue samples, were collected from 33 gastric cancer patients who received immunotherapy at Zhongda Hospital, Southeast University from January 2020 to December 2024. The density of tertiary lymphoid structures (TLS) and expression patterns of CD3, CD20, PNAd, and BCL6 were systematically evaluated using hematoxylin-eosin (H&E) staining and immunohistochemical (IHC) analysis. Statistical analyses were performed to determine the associations between TLS characteristics and clinical outcomes, including objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: Patients in the TLS-high infiltration group (TLSHigh) demonstrated significantly better outcomes compared to that of the TLS-low group (TLSLow), with higher ORR (58.8% vs 18.8%, P=0.019), DCR (94.1% vs 37.5%, <0.001), and markedly prolonged median PFS (276 vs 67 days, P＜0.000 1). Similarly, the BCL6-high expression group (BCL6High) showed superior treatment responses versus the BCL6-low group (BCL6Low), with significantly higher ORR (64.7% vs 12.5%, P=0.002), DCR (100.0% vs 31.3%, P＜0.001), and extended PFS (P＜0.001). Univariate and multivariable Cox regression confirmed TLS infiltration level as an independent favorable prognostic factor for gastric cancer patients receiving immunotherapy (HR=0.147, 95% CI: 0.022-0.964, P=0.046). Receiver operating characteristic (ROC) curve analysis revealed excellent predictive accuracy for both TLS infiltration [area under the curve (AUC)=0.885, P＜0.001] and the BCL6 scoring model (AUC=0.890, P＜0.001) in anticipating immunotherapy response. Conclusion: TLS density and BCL6 expression may serve as dual predictive and prognostic biomarkers for gastric cancer immunotherapy, highlighting their clinical utility in patient stratification and treatment guidance.