Abstract 5622: Acquired resistance to EGFR-TKI upregulates the expression of PD-L1 and promotes immune escape in lung cancer

Abstract

Abstract Background and purpose: Acquired resistance is a severe problem of EGFR inhibitors (EGFR-TKIs) therapy in lung cancer patients. Immune checkpoint therapy is a new revolution in cancer treatment with dramatic outcomes in a subset of patients. In this study, we explored the possibility of immune checkpoint therapy in lung cancers with three well-known resistant mechanisms to EGFR-TKIs, T790M, MET amplification and hepatocyte growth factor (HGF), and investigated internal regulation mechanisms. Experimental Design: PD-L1 expression and immune escape ability were evaluated in EGFR-TKIs resistant lung cancer cells by MET amplification, HGF, and T790M, as well as T790M transfected-human renal derived cells (293FT). MAPK and PI3K pathways were investigated simultaneously. PD-L1 gene deleted resistant cells were used in NOD-SCID xenograft models to evaluate immune escape in vivo. Results: All of three resistant mechanisms increased PD-L1 expression. Both MAPK and PI3K pathways are involved in MET amplification or HGF induced PD-L1 overexpression, whereas only MAPK pathway mediated it in T790M-transfected cells. The decreased cytotoxicity of lymphocytes can be restored by anti-PD-L1 antibodies. Moreover, xenograft tumors by EGFR-TKIs sensitive cells but not resistant cells responded to treatment of human lymphocytes. However, deletion of PD-L1 successfully restored cytotoxicity of lymphocytes in EGFR-TKIs resistant tumors. Conclusion: Acquired Resistance to EGFR-TKIs augments the expression of PD-L1 and promotes immune escape in EGFR mutant lung cancer. Immune checkpoint therapy might be a promising alternative therapeutic strategy for NSCLC that acquired resistant to EGFR-TKIs. Note: This abstract was not presented at the meeting. Citation Format: Shunli Peng, Qi Li, Wei Wang. Acquired resistance to EGFR-TKI upregulates the expression of PD-L1 and promotes immune escape in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5622. doi:10.1158/1538-7445.AM2017-5622