Abstract 887: The effect of anticancer chemotherapeutics on immune microenvironment of lung adenocarcinoma with EGFR mutation in vivomicroenvironment of lung adenocarcinoma with EGFR mutation in vivo

Abstract Lung cancer is the leading cause of cancer related deaths worldwide. Molecular targeting therapy is an attractive treatment for lung cancer, although it eventually develops resistance in most cases. In this report, we tested taxan antitumor effect on lung adenocarcinomas in vitro and in vivo. It could inhibit cell growth of many NSCLC cells tested, exhibiting reduced expression of c-MET and STAT3. The nascent effect of taxan on lung tumor cells were also proved on patient-derived primary lung tumor cells and patient-derived xenograft model that highly expresses c-MET. The antitumor effect of this chemotherapeutics was also observed on T790M mutant cells. Interestingly, the antitumor effect of taxan was synergistic in combination of c-Met inhibitor on lung tumor cells as well as patient-derived primary lung tumor cells. However, single treatment of taxan was sufficient for halting tumor growth in vivo, as no combinational effect of c-Met inhibitor was obvious. Not only c-Met inhibitor but also taxan reduced phosphorylated c-MET and STAT3, although cytokines on downstream of c-MET and STAT3 were explosively increased in vitro setting resulting in high expression of chemokines/cytokines. Importantly, the effect was not true in in vivo setting, in which the expressions of chemokines/cytokines as well as phosphorylated c-MET and STAT3 were influenced with this agent. These results suggest that taxane is one of the comparative adjuvant for lung tumors exhibiting targeted drug resistance, especially for enhanced signaling of MET-STAT-immuno-microenvironment. Citation Format: Young-Ah Suh, Hyemin Mun, Sun-Hye Lee, Se-Young Jo, Ju-Hee Oh, Chu-Hee Lee. The effect of anticancer chemotherapeutics on immune microenvironment of lung adenocarcinoma with EGFR mutation in vivomicroenvironment of lung adenocarcinoma with EGFR mutation in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 887.