FOXP3+ Cells in Tertiary Lymphoid Structures Have Adverse Impact on Overall Survival in Patients with Gastric Cancer

<b>Background/Objectives</b>: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). <b>Methods</b>: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8⁺ T cells and regulatory FOXP3⁺ T cells was analyzed. <b>Results</b>: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (<i>p</i> = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (<i>p</i> = 0.014 and <i>p</i> = 0.034). Mature TLSs had a higher FOXP3⁺ T lymphocyte density and lower CD8⁺/FOXP3⁺ ratio than immature TLSs (<i>p</i> = 0.029 and <i>p</i> = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (<i>p</i> = 0.033). In patients with TLS-positive GC, cases with FOXP3⁺ T cells had a shorter OS, 12.7 months vs. 47.5 months (<i>p</i> < 0.001). <b>Conclusions</b>: The presence of FOXP3⁺ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC.