AbstractAimsWe investigated the clinical implications and molecular features of TLS in stage I lung adenocarcinoma (LUAD).MethodsWe retrospectively reviewed the clinicopathological characteristics of 540 patients withp‐stage I LUAD. Logistic regression analysis was applied to determining the relationships between clinicopathological features and the presence of TLS. TLS‐associated immune infiltration pattern and signature genes were characterized using the transcriptomic profiles of 511 LUADs from The Cancer Genome Atlas (TCGA) database.ResultsThe presence of TLS was associated with a higher pT stage, low‐ and middle‐grade patterns, and the absence of tumor spreading through air spaces (STAS) and subsolid nodules. Multivariate Cox regression analysis identified that the presence of TLS was associated with favorable overall survival (OS) (p< 0.001) and recurrence‐free survival (RFS) (p< 0.001). Subgroup analysis showed that the most favorable OS (p< 0.001) and RFS (p< 0.001) favored the TLS + PD‐1‐ subgroup. The presence of TLS was characterized by abundance in antitumor immunocytes including activated CD8+ T and B cells as well as dentritic cells in TCGA cohort.ConclusionThe presence of TLS was an independent favorable factor for patients with stage I LUAD. The presence TLS was featured by special immune profiles which might aid oncologists in determining personalized adjuvant treatment.