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

doi:10.21037/tlcr.2019.11.17

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

Transl Lung Cancer Res. 2019 Dec;8(6):895-906. doi: 10.21037/tlcr.2019.11.17.

Authors

Keyi Jia^{1

2}, Yayi He¹, Rafal Dziadziuszko³, Sha Zhao^{1

2}, Xiaoshen Zhang^{1

2}, Juan Deng^{1

2}, Hao Wang^{1

2}, Fred R Hirsch⁴, Caicun Zhou¹, Hui Yu⁴, Liping Zhang⁵

Affiliations

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.

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).