Characterization of TCF‐1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients

Abstract

AbstractBackgroundT cell factor‐1 (TCF‐1) + stem‐like tumor‐infiltrating lymphocytes (stem‐like TILs) are important memory cells in the tumor microenvironment. However, their relationship with clinicopathological features, CD8+ TIL densities, immune checkpoint inhibitors (ICs), and prognostic values remain unknown for lung adenocarcinomas (LUADs). In this study, we aimed to characterize TCF‐1+ TILs and their prognostic significance in patients with surgically resected LUADs.MethodsExpression of TCF‐1, CD8, and ICs including programmed death‐1 (PD‐1), lymphocyte activating‐3 (LAG‐3), and T cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3) in TILs were estimated using immunohistochemistry of resected LUADs. The association between TCF‐1 expressions and clinicopathological characteristics of patient prognoses were analyzed.ResultsPositive TCF‐1 expression significantly correlated with advanced pathological stage, tumor grade, CD8+ TILs density, TIM‐3 expression, LAG‐3 expression, and PD‐1 expression. TCF‐1 positivity was significantly associated with a better recurrence‐free survival (RFS), and overall survival (OS). Subgroup analysis revealed that the TCF‐1+/CD8+ group had the best RFS and OS, while the TCF‐1‐/CD8‐ group had the worst RFS and OS. Similarly, patients with TCF‐1 + PD‐1‐ had the best prognoses and patients with TCF‐1‐PD‐1+ had the worst prognoses.ConclusionTCF‐1 had relatively high positive expression and special clinicopathological features in patients with LUAD. TCF‐1+ TILs were related to CD8 density, TIM‐3 expression, LAG‐3 expression, and PD‐1 expression, and were associated with better prognoses in LUAD patients. A combination of TCF‐1 and CD8 densities or PD‐1 expression further stratified patients into different groups with distinct prognoses.