Computerized tertiary lymphoid structures density on H&E-images is a prognostic biomarker in resectable lung adenocarcinoma

The increased amount of tertiary lymphoid structures (TLSs) is associated with a favorable prognosis in patients with lung adenocarcinoma (LUAD). However, evaluating TLSs manually is an experience-dependent and time-consuming process, which limits its clinical application. In this multi-center study, we developed an automated computational workflow for quantifying the TLS density in the tumor region of routine hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). The association between the computerized TLS density and disease-free survival (DFS) was further explored in 802 patients with resectable LUAD of three cohorts. Additionally, a Cox proportional hazard regression model, incorporating clinicopathological variables and the TLS density, was established to assess its prognostic ability. The computerized TLS density was an independent prognostic biomarker in patients with resectable LUAD. The integration of the TLS density with clinicopathological variables could support individualized clinical decision-making by improving prognostic stratification.