T cell immunoglobulin and mucin-domain containing-3 in non-small cell lung cancer

Keyi Jia, Yayi He, Rafal Dziadziuszko, Sha Zhao, Xiaoshen Zhang, Juan Deng, Hao Wang, Fred R. Hirsch, Caicun Zhou, Hui Yu, Liping Zhang

Abstract

Background: Immunotherapy has shown promising effect for non-small cell lung cancer (NSCLC) patients. Yet the biomarkers for predicting immunotherapy efficiency are still lacking.
Methods: We tested 139 surgical resected NSCLC primary tumor samples from Medical University of Gdansk, Poland, for T cell immunoglobulin and mucin-domain containing-3 (TIM-3) level by immunohistochemistry (IHC), analyzed the expression of TIM-3 protein on NSCLC tumor cells and tumor infiltrating lymphocytes (TILs).
Results: TIM-3 on TILs was correlated with programmed cell death protein-1 (PD-1) on TILs (correlation coefficient =0.346, P<0.001) and programmed cell death protein-ligand 1 (PD-L1) on TILs (correlation coefficient =0.313, P<0.001), PD-L1 level on tumor cells (correlation coefficient =0.255, P=0.002), TIM-3 level on tumor cells (correlation coefficient =0.262, P=0.002) and TIL percentage (correlation coefficient =0.172, P=0.043). TIM-3 level on tumor cells only had correlation with PD-L1 level (correlation coefficient =0.170, P=0.045). High level of TIM-3 on TILs indicated shorter recurrence-free survival (RFS) and overall survival (OS) (RFS 1.800 years, 95% CI, 1.230–2.370 vs. 0.870 years, 95% CI, 0.212–1.528, P=0.048) (OS 2.960 years, 95% CI, 2.268–3.652 vs. 1.080 years, 95% CI, 0.228–1.932, P=0.034).
Conclusions: TIM-3 is expressed on NSCLC tumor cells and TILs in all NSCLC pathological type. TIM-3 level on TILs had correlation with PD-1 and PD-L1 level. NSCLC patients with high TIM-3 level on TILs were more likely to have poor prognosis.