Abstract B71: Circulating PD-1+CD8+T cells reflect response to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer patients

Abstract

Abstract The programmed death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) pathway plays a crucial role in tumor evasion. Alteration in Epidermal Growth Factor Receptor (EGFR) and KRAS are oncogenic drivers in lung cancer and activation of this pathway is a critical event during lung tumorigenesis. However, how this oncogenic signaling influences immunity in the tumor microenvironment is just beginning to be understood. According to other report, expression of mutant EGFR in bronchial epithelial cells induces PD-L1 and PD-L1 expression is reduced by EGFR inhibitors in lung cancer cell lines with activated EGFR mutation. Thus, we evaluated the levels of PD-1+ T cells in peripheral blood according to the response of EGFR Tyrosine Kinase Inhibitors (TKIs) in Non-small Cell Lung Cancer (NSCLC) patients. Blood samples of NSCLC patients were obtained at baseline and after EGFR TKI treatment. Flow cytometry was used to detect PD-1 expressing CD4 or CD8 T cells. Total 53 patients were enrolled in the study. 17 patients had EGFR mutation and treated with EGFR TKIs. The expression of PD-1+CD8+ T cells in peripheral blood are increased according to their clinical stage. The expression levels of PD-1+CD8+ T cells significantly decreased after EGFR TKIs treatment (pretreatment vs. post-treatment 0.93±1.25% vs. 0.43±0.59%, P=0.006). Post/pre EGFR TKIs treatment ratio of PD-1+CD8+ T cells was lower in partial response group than stable disease group (0.19±0.17 vs. 0.9±0.68, P=0.017). So this result showed that PD-1+CD8+ T cells was more decreased in good responder group. EGFR mutant lung tumor inhibited antitumor immunity by activating PD-1 and PD-1 expression was reduced by EGFR TKI, which was proportional to treatment response. In conclusion, the change of PD-1+CD8+ T cell in peripheral blood may be a surrogate marker to predict EGFR TKIs treatment response. Citation Format: Sung Yong Lee, Sungjong Lee, Jee Youn Oh, Kyung Hoon Min, Gyu Young Hur, Jae Jeong Shim, Kyung Ho Kang. Circulating PD-1+CD8+T cells reflect response to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B71.