Prognostic Impact and Clinicopathological Significance of TIM ‐3 and LAG ‐3 Expressions in Laryngeal Squamous Cell Carcinoma

ABSTRACT Introduction Research on immune checkpoint molecules is increasing, reflecting their critical role in cancer pathogenesis. While PD‐1, PD‐L1, and CTLA‐4 have been widely studied in head and neck cancers, outcomes remain unsatisfactory, highlighting the need for novel prognostic markers and therapeutic targets. This study evaluated the prognostic significance of TIM‐3 and LAG‐3 expressions in laryngeal squamous cell carcinoma. Methods Fifty patients who underwent open partial or total laryngectomy for laryngeal squamous cell carcinoma (2016–2018) were retrospectively analyzed. Tumor specimens were assessed by immunohistochemistry for TIM‐3 and LAG‐3 expressions, as well as overall immune infiltration. Survival analyzes were performed using Kaplan–Meier and multivariable Cox regression models. Results TIM‐3 expression showed no significant prognostic impact in the overall cohort but was associated with worse overall survival in the low‐to‐moderate immune infiltration subgroup ( p = 0.045). LAG‐3 positivity correlated with reduced recurrence‐free survival in the full cohort ( p = 0.015) and with both overall and recurrence‐free survival in the low/moderate infiltration subgroup ( p = 0.029 and p = 0.016, respectively). Multivariable Cox regression suggested LAG‐3 as an independent predictor of recurrence, while TIM‐3 showed an effect on overall survival only in the low/moderate immune infiltration subgroup. Conclusion TIM‐3 and LAG‐3 expressions are associated with adverse outcomes in laryngeal cancer, particularly in tumors with limited immune infiltration. These findings are exploratory and support further multicenter studies to validate their prognostic and potential immunotherapeutic relevance. Level of Evidence 3.