# Pan-cancer analysis of ALK mutation and its association with tumor immunogenicity and the efficacy of immune checkpoint blockade

## TL;DR

This study finds that ALK mutations are linked to better survival in cancer patients undergoing immunotherapy, suggesting they could help guide treatment decisions.

## Contribution

The study introduces a nomogram for predicting immunotherapy outcomes and shows ALK mutations enhance tumor immunogenicity.

## Key findings

- ALK mutation is associated with improved overall survival in patients receiving immune checkpoint inhibitors.
- ALK mutation increases immune cell infiltration and tumor immunogenicity.
- A nomogram was developed to estimate 12- and 24-month survival probabilities after immunotherapy.

## Abstract

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.