Cheng Lin1, Xiong Chen1, Meifang Li2, Jingnan Liu1, Xingfeng Qi3, Wenting Yang3, Hairong Zhang4, Zhongfu Cai5, Yun Dai6, Xuenong Ouyang7. 1. Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China. 2. Department of Oncology, Fujian Provincial Cancer Hospital, Jinan District, Fuzhou, Fujian, China. 3. Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China. 4. Department of Epidemiology and Health Statistics, Fujian Medical University School of Public Health, Fuzhou, Fujian, China. 5. Department of Oncology, 180th Hospital of People's Liberation Army, Quanzhou, Fujian, China. 6. Division of Hematology and Oncology, Department of Medicine, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA. 7. Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China. Electronic address: oyxn@public.fz.fj.cn.
Abstract
BACKGROUND: The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven non-small-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-L1 expression in patients with the subtype of NSCLC carrying EGFR mutations remain limited. MATERIALS AND METHODS: Immunohistochemistry was performed to evaluate the expression of PD-1, PD-L1, and CD4+ and CD8+ tumor-infiltrating T lymphocytes (TILs). RESULTS: In a cohort of 56 patients, PD-L1 and PD-1 was positive in 53.6% and 32.1% of tumor specimens, respectively. PD-L1(+) patients had a significantly greater disease-control rate (P = .004), in association with longer progression-free survival (P = .001) after EGFR-tyrosine kinase inhibitor (TKI) therapy and overall survival (P = .004), and no correlation between PD-1 positivity and clinical outcomes was observed. PD-L1 expression was not significantly associated with either clinicopathologic features or TILs. CONCLUSIONS: These findings suggest that this subtype of EGFR mutation-positive NSCLC is highly eligible for PD-1/PD-L1 immunotherapy. PD-L1 might represent a favorable biomarker candidate for the response to EGFR-TKIs and outcomes of these patients with NSCLC.
BACKGROUND: The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven non-small-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-L1 expression in patients with the subtype of NSCLC carrying EGFR mutations remain limited. MATERIALS AND METHODS: Immunohistochemistry was performed to evaluate the expression of PD-1, PD-L1, and CD4+ and CD8+ tumor-infiltrating T lymphocytes (TILs). RESULTS: In a cohort of 56 patients, PD-L1 and PD-1 was positive in 53.6% and 32.1% of tumor specimens, respectively. PD-L1(+) patients had a significantly greater disease-control rate (P = .004), in association with longer progression-free survival (P = .001) after EGFR-tyrosine kinase inhibitor (TKI) therapy and overall survival (P = .004), and no correlation between PD-1 positivity and clinical outcomes was observed. PD-L1 expression was not significantly associated with either clinicopathologic features or TILs. CONCLUSIONS: These findings suggest that this subtype of EGFR mutation-positive NSCLC is highly eligible for PD-1/PD-L1 immunotherapy. PD-L1 might represent a favorable biomarker candidate for the response to EGFR-TKIs and outcomes of these patients with NSCLC.
Authors: Edwin R Parra; Carmen Behrens; Jaime Rodriguez-Canales; Heather Lin; Barbara Mino; Jorge Blando; Jianjun Zhang; Don L Gibbons; John V Heymach; Boris Sepesi; Stephen G Swisher; Annikka Weissferdt; Neda Kalhor; Julie Izzo; Humam Kadara; Cesar Moran; Jack J Lee; Ignacio I Wistuba Journal: Clin Cancer Res Date: 2016-06-01 Impact factor: 12.531