Mutation of neurotrophic tyrosine receptor kinase can promote pan-cancer immunity and the efficacy of immunotherapy.

ABSTRACT

The Neurotrophic tyrosine receptor kinase (NTRK) family plays important roles in tumor progression and is involved in tumor immunogenicity. Here, we conducted a comprehensive bioinformatic and clinical analysis to investigate the characteristics of NTRK mutations and their association with the outcomes in pan-cancer immunotherapy. In 3888 patients across 12 cancer types, patients with NTRK-mutant tumors showed more benefit from immunotherapy in terms of objective response rate (ORR; 41.7% vs. 27.5%; P < 0.001), progress-free survival (PFS; HR = 0.80; 95% CI, 0.68-0.96; P = 0.01), and overall survival (OS; HR = 0.71; 95% CI, 0.61-0.82; P < 0.001). We further constructed and validated a nomogram to estimate survival probabilities after the initiation of immunotherapy. Multi-omics analysis on intrinsic and extrinsic immune landscapes indicated that NTRK mutation was associated with enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, NTRK mutation may promote cancer immunity and indicate favorable outcomes in immunotherapy. Our results have implications for treatment decision-making and developing immunotherapy for personalized care.