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.

中文翻译：

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神经营养性酪氨酸受体激酶突变可促进泛癌免疫及免疫治疗疗效

神经营养性酪氨酸受体激酶（NTRK）家族在肿瘤进展中发挥重要作用，并参与肿瘤免疫原性。在这里，我们进行了全面的生物信息学和临床分析，以研究 NTRK 突变的特征及其与泛癌免疫治疗结果的关联。在 12 种癌症类型的 3888 名患者中，NTRK 突变肿瘤患者在客观缓解率（ORR；41.7% vs. 27.5%；P < 0.001）、无进展生存期（PFS；HR = 0.80）方面显示出更多从免疫治疗中获益；95% CI，0.68–0.96；P = 0.01）和总生存期（OS；HR = 0.71；95% CI，0.61–0.82；P < 0.001）。我们进一步构建并验证了列线图，以估计免疫治疗开始后的生存概率。对内在和外在免疫景观的多组学分析表明，NTRK 突变与肿瘤免疫原性增强、免疫细胞浸润丰富和免疫反应改善有关。总之，NTRK 突变可能会促进癌症免疫并预示着免疫治疗的良好结果。我们的结果对治疗决策和开发个性化护理的免疫疗法具有影响。