Non-Small Cell Lung Cancer (NSCLC) harboring Anaplastic Lymphoma Kinase (ALK) gene rearrangements is successfully treated with ALK tyrosine kinase inhibitors (TKIs) for only a limited amount of time as most cases relapse due to the development of drug resistance. Here we show that a vaccine against ALK induced a strong and specific immune response that impaired the growth of ALK-positive lung tumors in mouse models prophylactically and therapeutically. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. Furthermore, we demonstrated that ALK-rearranged lung tumors induce an immunosuppressive microenvironment and that oncogenic ALK regulates the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy that, however, was restored by administration of anti-PD-1 antibody. Thus, combination of ALK vaccine with TKIs and immune checkpoint blockade therapy might represent a powerful strategy for the treatment of ALK-driven NSCLC.
- Received April 2, 2015.
- Revision received June 2, 2015.
- Accepted July 23, 2015.
- Copyright © 2015, American Association for Cancer Research.