Keyi Jia1,2, Yayi He1, Rafal Dziadziuszko3, Sha Zhao1,2, Xiaoshen Zhang1,2, Juan Deng1,2, Hao Wang1,2, Fred R Hirsch4, Caicun Zhou1, Hui Yu4, Liping Zhang5. 1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China. 2. School of Medicine, Tongji University, Shanghai 200433, China. 3. Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland. 4. Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora 80045, CO, USA. 5. Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
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. 2019 Translational Lung Cancer Research. All rights reserved.
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. 2019 Translational Lung Cancer Research. All rights reserved.
Entities:
Keywords:
Non-small cell lung cancer (NSCLC); T cell immunoglobulin and mucin-domain containing-3 (TIM-3); programmed cell death protein-1 (PD-1); programmed cell death protein-ligand 1 (PD-L1); tumor infiltrating lymphocytes (TILs)
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