Effects of anti-PD-L1 monoclonal antibody and EGFR-TKI on the expression of PD-L1 and function of T lymphocytes in EGFR-mutated lung cancer cells
10.3760/cma.j.issn.0253-3766.2016.12.002
- VernacularTitle:抗程序性死亡配体1单抗和表皮生长因子受体酪氨酸激酶抑制剂对表皮生长因子受体敏感突变肺癌细胞中程序性死亡配体1表达和T细胞功能的影响
- Author:
You SHE
1
;
Xue PAN
;
Yufei XING
;
Tong ZHOU
;
Zengli ZHANG
;
Minhua SHI
;
Yongjing CHEN
Author Information
1. 215004,苏州大学附属第二人民医院呼吸内科
- Keywords:
Subject words] Lung neoplasms;
Epidermal growth factor receptor,EGFR;
Programmed death-ligand 1;
T lymphocytes;
Cellular immunity;
Erlotinib
- From:
Chinese Journal of Oncology
2016;38(12):886-892
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of anti?PD?L1 monoclonal antibody and EGFR?TKI on expression of soluble PD?L1 and function of T lymphocytes in EGFR?mutated lung cancer cells. Methods Flow cytometry was used to analyze the expression of membrane PD?LI. ELISA was performed to detect the level of sPD?L1 in the supernatant of cultured EGFR?mutated and wild type lung cancer cells before and after erlotinib treatment. After treated with anti?PD?L1 monoclonal antibody alone and in combination with erlotinib, the proliferation of T lymphocytes in co?culture system was measured using Cell Counting Kit?8 ( CCK?8) assay. The expression levels of PD?LI and IFN?γin tumor cells and T lymphocytes treated with erlotinib in co?culture system were analyzed by flow cytometry and ELISA, respectively. Results PD?L1 was highly expressed in EGFR?mutated lung cancer PC9 cells (78.7±3.1)% and HCC827 cells (82. 7±2.6)%.After treated with erlotinib, the expression rates of membrane PD?L1 in PC9 and HCC827 cells were down?regulated (64.7%±3.1% and 73.0%±2.6%, respectively),significantly lower than that in the two cell lines without erlotinib treatment ( P<0.05) , and the expression levels of sPD?L1 in the supernatant of PC9 and HCC827 cells were also down?regulated ( 0. 680 ± 0. 120) ng/ml and ( 0. 903 ± 0. 047) ng/ml, respectively, significantly lower than that in the two cell lines without erlotinib treatment ( P<0. 01 ) . However, no significant changes of membrane PD?L1 and sPD?L1 expression were found in EGFR wild type lung cancer cells ( H1299 and A549) before and after erlotinib treatment. In the co?culture system composed of T cells and EGFR?mutated lung cancer cells, treatment with erlotinib alone promoted the proliferation of T lymphocytes (P<0.05), and combined treatment of anti?PD?L1 monoclonal antibody with erlotinib had a stronger effect ( P<0.05) . In the co?culture system composed of T cells and EGFR wild type cell lines, the proliferation of T cells was not changed after using erlotinib alone or combination of erlotinib and anti?PD?L1 monoclonal antibody ( P>0.05) . Before and after treatment with erlotinib, the secretion levels of IFN?γwere (856.0± 70. 3) pg/ml and ( 1 697. 3 ± 161. 0) pg/ml, respectively, showing a significant difference ( P<0.001). The expression rates of membrane PD?L1 were (76.2±0.5)% and (50.9±0.9)%, respectively, also showing a significant difference ( P<0.001) . However, no significant changes in the expression of IFN?γ and membrane PD?L1 were found in the co?culture system composed of T cells and A549 cells. Conclusions Anti?PD?L1 monoclonal antibody combined with EGFR?TKI can effectively promote the proliferation and secretion function of T lymphocytes in the microenvironment of EGFR?mutated lung cancer cells.
