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

Kamya Sankar; Sunitha Nagrath; Nithya Ramnath

doi:10.3390/cancers13061476

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

Cancers (Basel). 2021 Mar 23;13(6):1476. doi: 10.3390/cancers13061476.

Authors

Kamya Sankar¹, Sunitha Nagrath^{2

3}, Nithya Ramnath⁴

Affiliations

¹ Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-5848, USA.
² Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109-5848, USA.
³ Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109-5848, USA.
⁴ Division of Medical Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48109-5848, USA.

Abstract

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.

Keywords: ALK; ALK-rearrangements; cancer vaccine; immune evasion; immunotherapy; non-small cell lung cancer; tyrosine kinase inhibitors.

Publication types

Review