Background: Approximately 20-30% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutations are not responsive to EGFR-tyrosine kinase inhibitors (TKIs). Although, primary resistance to EGFR-TKI is attributed to various genetic alterations, little is known about the clinical and immunopathological features of patients with primary resistance. The tumor immune microenvironment including tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) has been reported to play an important role in tumor progression in NSCLC. However, few studies have directly focused on the relationship between the tumor immune microenvironment and primary resistance to EGFR-TKI.

Materials and Methods: Characteristics of 124 NSCLC patients with EGFR mutations who received EGFR-TKI were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFR-TKI treatment were assessed for the density of TILs expressing CD4 or CD8, and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically.

Results: Primary resistance was observed in 13.7% (17/124) of patients. Smoking Tobacco correlated significantly with primary resistance compared to non-primary resistance. Lower density of total TILs and negative PD-L1 expression as per immunohistochemical analysis correlated significantly with primary resistance. Moreover, immune ignorant phenotype of tumor microenvironment, negative PD-L1 expression with low TIL density, was significantly observed in primary resistance.

Conclusions: Smoking and immune ignorance in the tumor microenvironment might result in primary resistance to EGFR-TKIs.

Citation Format: Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C. Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura. Clinicopathologic features and immune microenvironment of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors [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 3927.