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

BACKGROUND: T 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. METHODS: Expression 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. RESULTS: Positive 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. CONCLUSION: TCF‐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.