Pan-cancer analysis of MET mutation and its association with the efficacy of immune checkpoint blockade

The mesenchymal-epithelial transition factor (<i>MET</i>) proto-oncogene plays important roles during tumor development. Recently, evidence has revealed <i>MET</i> signaling may impact tumor immunogenicity and regulate the immune response. Here we conducted a comprehensive bioinformatic and clinical analysis to explore the characteristics of <i>MET</i> mutation and its association with the outcomes in pan-cancer immunotherapy. In 4149 patients with 12 tumor types treated with immune checkpoint inhibitors, <i>MET</i> mutation indicated favorable overall survival (hazard ratio = 0.61; 95% CI, 0.50-0.74; <i>P</i> < 0.001), progression-free survival (hazard ratio = 0.74; 95% CI, 0.60-0.92; <i>P</i> = 0.01), and objective response rate (40.3% <i>vs</i>. 28.1%; <i>P</i> = 0.003). Moreover, we developed a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy. Further multi-omics analysis on both intrinsic and extrinsic immune landscapes revealed that <i>MET</i> mutation enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, <i>MET</i> mutation improves cancer immunity and is an independent biomarker for favorable outcomes in pan-cancer immunotherapy. These results may influence clinical practices, guide treatment decision-making, and develop immunotherapy for personalized care.