Abstract 7204: Stimulator of interferon genes (STING) protein expression in resected non-small cell lung cancer with EGFR mutation

Abstract Background and Objective: In lung cancer with epidermal growth factor receptor (EGFR) mutations (mEGFR), the expression of programmed death-ligand 1 (PD-L1), a predictive marker for the efficacy of immune checkpoint inhibitors (ICI), is generally low, and the effectiveness of ICIs is considered limited. However, a subset of mEGFR cases exhibits high PD-L1 expression, and in such cases, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have been reported to show reduced efficacy. PD-L1 expression in lung cancer tissue can result from tumor immune responses against neoantigens but may also be induced by the initial immune response via the stimulator of interferon genes (STING) pathway. Moreover, ICI efficacy is reported to be poor in STING-deficient mice. This study, therefore, aimed to analyze the relationship between STING expression and clinicopathological factors, PD-L1 expression, and prognosis in resected mEGFR cases. Materials and Methods: This study included 40 cases of mEGFR-positive lung cancer surgically resected at our institution between November 2018 and May 2020. Immunohistochemical staining of tumor tissues was performed using an anti-STING antibody (D2P2F), and expression levels were evaluated using the H-score method. EGFR amplification was assessed by qPCR. Results: Among the 40 cases, 29 were female, with a median age of 72.5 years (range: 42-84 years), and 25 were never-smokers. Pathological stages included stage I in 36 cases and stage III in 4 cases. The EGFR mutation types comprised exon 19 deletions in 16 cases, L858R in 17 cases, and other mutations in 7 cases. PD-L1 expression was negative in 16 cases, 1-49% in 20 cases, and high (≥50%) in 4 cases. STING was expressed in the cytoplasm of tumor cells, with a median H-score of 180 (range: 50-290). When cases were classified into high and low STING expression groups using a cutoff H-score of 150, no significant differences in clinicopathological factors or PD-L1 expression were observed between the two groups. However, a significant correlation was noted between STING expression and EGFR copy number. Prognostic analysis revealed that the high STING expression group had significantly worse outcomes compared to the low expression group (5-year recurrence-free survival: 93% vs. 56%, p = 0.038). Discussion: High STING expression was identified as a poor prognostic factor in mEGFR cases. STING expression correlated with EGFR copy number, suggesting that EGFR copy number may influence STING expression and the malignancy of mEGFR. Further studies are required to investigate the impact of EGFR copy number on STING expression and the malignant potential of mEGFR. Citation Format: Atsushi Osoegawa, Yohei Takumi, Kento Inoue, Eika Kudo, Kazuki Ota, Yuta Abe, Takahiro Sato, Daiki Noda, Miyuki Abe, Naoki Haratake, Kenji Sugio. Stimulator of interferon genes (STING) protein expression in resected non-small cell lung cancer with EGFR mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7204.