c-MET expression and immune landscape in locally advanced patients with non-small cell lung cancer undergoing radiochemotherapy and consolidative immunotherapy

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Background: The mesenchymal-epithelial transition factor (MET) gene is a key therapeutic target in non-small cell lung cancer (NSCLC), affecting the tumor expression of programmed cell death ligand 1 (PD-L1) and the immune microenvironment. This study examined the relationship between cellular MET (c-MET) expression, immune profiles, and survival in patients with NSCLC treated with radiochemotherapy and consolidative immunotherapy. Methods: c-MET expression levels and immune profiles, including cluster of differentiation 8 (CD8), cluster of differentiation 68 (CD68), lymphocyte-activation gene 3 (LAG3), forkhead box protein P3 (FOXP3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), were accessed in 60 locally advanced patients with NSCLC treated with radiochemotherapy and sequential immunotherapy at Shanghai Pulmonary Hospital. Correlations between c-MET gene expression and immune cell infiltration were additionally explored using publicly available transcriptomic datasets and bioinformatics analysis. Categorical data were analyzed with Chi-squared tests, survival functions were derived from Kaplan-Meier estimates, and Cox regression assessed the independent impact on overall survival (OS) and progression-free survival (PFS). Results: PFS and OS for the cohort were 24.0 and 34.0 months, respectively. OS was significantly associated with reduced macrophage (CD68+) infiltration (P=0.03), while PFS was significantly associated with high c-MET expression (P=0.03). Correlation analysis indicated a significant correlation between c-MET expression and macrophage (CD68+) infiltration (P=0.01). Conclusions: c-MET expression and macrophage (CD68+) infiltration were identified as potential predictors of survival and were found to be significantly correlated with one another. These findings suggest that antibody-drug conjugates targeting c-MET in combination with immune checkpoint inhibitors may represent a potentially effective consolidation therapy strategy following chemoradiotherapy in patients with locally advanced NSCLC.

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