Increased LAG-3, TIM-3, and IDO1 Expression Is Associated With Oral Squamous Cell Carcinoma in Never Smokers and Never Drinkers.
[BACKGROUND] Immune checkpoints such as, LAG-3, TIM-3, and IDO1 have emerged as potential therapeutic targets beyond PD-1/PD-L1 blockade.
- p-value p ≤ 0.039
- p-value p ≤ 0.015
APA
Fiedler M, Off A, et al. (2026). Increased LAG-3, TIM-3, and IDO1 Expression Is Associated With Oral Squamous Cell Carcinoma in Never Smokers and Never Drinkers.. Oral diseases. https://doi.org/10.1111/odi.70301
MLA
Fiedler M, et al.. "Increased LAG-3, TIM-3, and IDO1 Expression Is Associated With Oral Squamous Cell Carcinoma in Never Smokers and Never Drinkers.." Oral diseases, 2026.
PMID
41853911
Abstract
[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.