Introduction:

Anaplastic Lymphoma Kinase (ALK) re-arrangements define a distinct molecular subset of non-small cell lung cancer (NSCLC) that predominantly affects younger patients and those with sparse or no smoking exposure. These patients do not derive significant clinical benefit from currently available immune checkpoint inhibitors. Elucidating the mechanisms underlying the immunosuppressive tumor microenvironment will help inform the development novel immunotherapy approaches for ALK+ NSCLC.

Conclusion:

Despite high levels of PD-L1, ALK+ tumors exhibit multiple features of an inert immune TME, primarily characterized by low TMB and decreased CD8+ T cells and immune activation markers. While immunosuppressive factors such as M2 macrophages and adenosine signaling may be targeted, strategies to enhance immunogenicity will be critical for an effective immune response in ALK+ NSCLC.