Tumor-associated tertiary lymphoid structure predicts postoperative outcomes in patients with primary gastrointestinal stromal tumors

Tumor-infiltrating tertiary lymphoid structures (TLS) are thought to have anti-tumor activity and are believed to indicate a favorable prognosis in cancer patients. However, the prognostic value of TLS in gastrointestinal stromal tumors (GIST) is unknown. We evaluated the prognostic value of TLS using two independent GIST cohorts. Pathological examinations identified TLS in 44.9% of patients in our discovery cohort (DC). TLS was significantly associated with smaller tumor size (P = .011), relatively well morphological classification (P < .001), lower NIH classification (P < .001), lower recurrence (P = .005), longer survival time (P < .001) and lower imatinib resistance (P = .006). Kaplan-Meier curves showed that TLS was remarkably associated with favorable survival (P = .0002) and recurrence (P = .0015) time. In addition, the presence of KIT mutations and the absence of TLS suggested worst prognosis both in terms of overall survival (OS) (P = .0029) and time to recurrence (TTR) (P = .0150), while the presence of PDGFRA mutations and TLS suggested optimal prognosis for OS and TTR. Multivariate analyzes demonstrated that TLS was an independent prognostic factor for OS (HR:0.180, P = .002) and TTR (HR:0.412, P = .023). These results were confirmed using our validation cohort. Multiplexed immunohistochemistry staining was used to determine the composition of TLS. Therapies designed to target TLS may be a novel therapeutic strategy for GIST patients with imatinib resistance.