(P 324) FULLY MATURE TERTIARY LYMHOID STRUCTURES AS PREDICTORS OF LOCAL RECURRENCE IN SOFT TISSUE SARCOMAS

Objective: Soft-tissue sarcomas (STS) are rare and heterogeneous malignancies with generally poor and unpredictable prognosis. Tertiary lymphoid structures (TLS) have been identified as favorable prognostic indicators in several cancer types, yet their specific role in STS remains poorly defined. This study investigates the prognostic relevance of TLS presence, maturity, location and semi-quantitative assessment of their density in resected primary STS.

Methods: We retrospectively analyzed 219 cases of primary STS surgically resected at the Bergonié Institute (Comprehensive Cancer Center of Bordeaux, France) between 1990 and 2020. TLS were assessed for presence, spatial distribution, semi-quantitative density and degree of maturity using CD20 and CD23 immunohistochemistry, categorizing tumors as fully mature TLS-positive (fmTLS⁺) or negative (fmTLS⁻). RNA sequencing was performed on 126 formalin-fixed paraffin-embedded samples to characterize immune microenvironment profiles. Survival outcomes—including overall survival (OS), time to locoregional progression (TTLRP), and time to distant progression (TTDP)—were analyzed using Kaplan-Meier estimates and Cox proportional hazards models.

Results: The presence of fmTLS was significantly associated with improved 5-year OS (p=0.012) and cause-specific survival (p=0.006). Unexpectedly, fmTLS⁺ tumors showed a higher rate of local recurrence (22.9% vs. 8.1%, p=0.002). On multivariate analysis, high-density fmTLS⁺ tumors conferred a 2.68-fold increased risk of locoregional progression (95% CI: 1.28-5.59, p=0.009). Transcriptomic profiling confirmed a significant correlation between fmTLS⁺ status and an high-immune phenotype (Φ=0.30, p< 0.001), supporting our pathological assessment.

Conclusion: The presence of fmTLS in STS are associated with favorable improved OS but paradoxically increased risk of local recurrence. These findings suggest that fmTLS could serve as a dual prognostic biomarker, highlighting the need for stratified surveillance and tailored adjuvant strategies in fmTLS⁺ patients.