Immunotherapy for ALK-Rearranged Non-Small Cell Lung Cancer: Challenges Inform Promising Approaches.

Rearrangements in the Anaplastic Lymphoma Kinase (ALK) gene have been implicated in 5-6% of all non-small cell lung cancers. ALK-rearranged non-small cell lung cancers are sensitive to ALK-directed tyrosine kinase inhibitors, but generally resistant to single-agent immune checkpoint inhibitors. Here, we aim to describe the mechanisms of ALK aberrations in non-small cell lung cancer by which an immunosuppressed tumor microenvironment is created, leading to host immune evasion. We report pre-clinical and clinical studies evaluating novel immunotherapeutic approaches and describe the promises and challenges of incorporating immune-based treatments for ALK-rearranged non-small cell lung cancer.