Abstract 11: Artificial intelligence-based spatial analysis of the local tumor microenvironment in relation to c-MET expression in non-small cell lung cancer.

Abstract Introduction: MET is a well-known oncogenic driver that confers various genomic aberrations. Recent approval of antibody drug conjugates has expanded therapeutic options for c-MET expressing non-small cell lung cancer (NSCLC). However, the relationship between MET expression, tumor microenvironment (TME), and immunotherapy response remains unclear. This study explores the association between c-MET expression and spatial TME features in NSCLC to better understand its immunologic behavior. Methods: This study analyzed a total of 25,674 NSCLC samples from various cohorts, including AACR GENIE, TCGA, Ajou University Medical Center (AUMC), and Agilent Technologies. AI-powered analyzers (Lunit SCOPE IO and SCOPE uIHC) were previously developed using 19,112 H0.001). TME analysis of samples with high (Z-score ≥2) and low RNA expression showed no significant difference in tumor-infiltrating lymphocyte (TIL) density (/mm2, median: 851 vs. 673, p=0.46). In 640 pairs of H Agilent, 80.6 vs. 211.3, p=0.23, respectively). This trend became significant with cell and subcellular spatial analysis. The density of TIL was markedly reduced within 30um of tumor cells exhibiting strong (3+) c-MET expression (median:85.5 vs. 121.6, p0.001; 132.2 vs. 162, p=0.013, respectively). Notably, a similar reduction in TIL density was also observed around tumor cells with membrane-specific c-MET expression (median: 106.6 vs. 122.3, p0.001; 144.9 vs. 165.8, p=0.002, respectively). Conclusion: Spatial analysis of IHC demonstrated sparse immune cells near tumor cells with strong c-MET expression or membrane-specific localization. These findings suggest a mechanistic link between c-MET overexpression and immune evasion, indicating the potential benefit of combining MET-targeted and immunotherapy. Citation Format: Ji-Hyang Lee, Joshua Littrell, Chiyoon Oum, Taebum Lee, Sanghoon Song, Yoojoo Lim, Chang Ho Ahn, Jim Christian, Seokwhi Kim, Siraj M. Ali. Artificial intelligence-based spatial analysis of the local tumor microenvironment in relation to c-MET expression in non-small cell lung cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 11.