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Войти в исследования Oral diseases · 2026
Increased LAG-3, TIM-3, and IDO1 Expression Is Associated With Oral Squamous Cell Carcinoma in Never Smokers and Never Drinkers.
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Fiedler Mathias, Off Alisa, Eichberger Jonas, Gottsauner Maximilian, Schuderer Johannes G, Maurer Michael, Eckmüller Stephanie, Himmelstoß Katja, Bauer Richard J, Gerken Michael, Reichert Torsten E, Weber Florian, Ettl Tobias
Аннотация
BACKGROUND: Immune checkpoints such as, LAG-3, TIM-3, and IDO1 have emerged as potential therapeutic targets beyond PD-1/PD-L1 blockade. Their expression patterns in oral squamous cell carcinoma, especially among patients without smoking or alcohol exposure, remain poorly understood.
METHODS: Immunohistochemical expression of LAG-3, TIM-3, and IDO1 was examined in 130 oral squamous cell carcinoma specimens. Expression levels were correlated with clinicopathological features, immune infiltration (CD4+, CD8+, FoxP3+, CD1a+), PD-1/PD-L1 status, and smoking and drinking history. Tumors co-expressing all checkpoints (LAG-3+/TIM-3+/IDO1+/PD-L1+) were classified as "comprehensive checkpoint-positive."
RESULTS: High LAG-3, TIM-3, and IDO1 expression was significantly associated with never-smoking/never-drinking status (p ≤ 0.039) and increased CD4+, CD8+, and FoxP3+ T-cell densities (p ≤ 0.015). All markers showed strong correlations with PD-1/PD-L1 and with each other (p ≤ 0.002). The comprehensive checkpoint-positive phenotype occurred in 16.8% of cases, more often in never-smoking/never-drinking patients (p = 0.011), females (p = 0.026), and well-differentiated tumors (p = 0.007).
CONCLUSION: Co-expression of LAG-3, TIM-3, and IDO1 characterizes an immune-active but potentially exhausted microenvironment, particularly in never-smoking, never-drinking oral squamous cell carcinoma. This pattern may define an immunologically distinct subtype with possible relevance for combinatorial immunotherapy approaches.
METHODS: Immunohistochemical expression of LAG-3, TIM-3, and IDO1 was examined in 130 oral squamous cell carcinoma specimens. Expression levels were correlated with clinicopathological features, immune infiltration (CD4+, CD8+, FoxP3+, CD1a+), PD-1/PD-L1 status, and smoking and drinking history. Tumors co-expressing all checkpoints (LAG-3+/TIM-3+/IDO1+/PD-L1+) were classified as "comprehensive checkpoint-positive."
RESULTS: High LAG-3, TIM-3, and IDO1 expression was significantly associated with never-smoking/never-drinking status (p ≤ 0.039) and increased CD4+, CD8+, and FoxP3+ T-cell densities (p ≤ 0.015). All markers showed strong correlations with PD-1/PD-L1 and with each other (p ≤ 0.002). The comprehensive checkpoint-positive phenotype occurred in 16.8% of cases, more often in never-smoking/never-drinking patients (p = 0.011), females (p = 0.026), and well-differentiated tumors (p = 0.007).
CONCLUSION: Co-expression of LAG-3, TIM-3, and IDO1 characterizes an immune-active but potentially exhausted microenvironment, particularly in never-smoking, never-drinking oral squamous cell carcinoma. This pattern may define an immunologically distinct subtype with possible relevance for combinatorial immunotherapy approaches.