Anaplastic lymphoma kinase (ALK) plays important roles in tumorigenesis and is involved in tumor immunogenicity through various pathways. Here, we conducted a comprehensive bioinformatic and clinical analysis on the characteristics of pan-cancer ALK mutation and its association with tumor immunity and the efficacy of immune checkpoint blockade. In 2930 patients with 11 tumor types treated with immune checkpoint inhibitors, the mutation of ALK indicated favorable overall survival (hazard ratio = 0.69; 95% confidence interval, 0.57–0.83; p < 0.001). We further developed and validated a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy. Moreover, multi-omics analysis on both intrinsic and extrinsic immune landscapes revealed that the mutation of ALK could enrich infiltration of immune cells, enhance tumor immunogenicity, and improve immune responses. In conclusion, ALK mutation is associated with promoted cancer immunity and can be treated as a biomarker for favorable outcomes in pan-cancer immune checkpoint blockade. These results have implications for treatment decision-making and developing immunotherapy for personalized care.

The mesenchymal-epithelial transition factor (MET) proto-oncogene plays important roles during tumor development. Recently, evidence has revealed MET signaling may impact tumor immunogenicity and regulate the immune response. Here we conducted a comprehensive bioinformatic and clinical analysis to explore the characteristics of MET mutation and its association with the outcomes in pan-cancer immunotherapy. In 4149 patients with 12 tumor types treated with immune checkpoint inhibitors, MET mutation indicated favorable overall survival (hazard ratio = 0.61; 95% CI, 0.50–0.74; P < 0.001), progression-free survival (hazard ratio = 0.74; 95% CI, 0.60–0.92; P = 0.01), and objective response rate (40.3% vs. 28.1%; P = 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 MET mutation enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, MET 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.