Targeting the MET gene: unveiling therapeutic opportunities in immunotherapy within the tumor immune microenvironment of non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) represents the most prevalent histological subtype of lung cancer. Within this disease, the MET gene emerges as a critical therapeutic target, exhibiting various forms of dysregulation. Although MET tyrosine kinase inhibitors, HGF/c-MET targeting antibodies, and antibody-drug conjugates constitute the primary treatment modalities for patients with MET-altered NSCLC, numerous questions remain regarding their optimal application. The advent of immunotherapy holds promise for enhancing therapeutic outcomes in patients with MET-altered NSCLC. MET mutations can reshape the tumor immune microenvironment of NSCLC by reducing tumor immunogenicity, inducing exhaustion in immune-activated cells, and promoting immune evasion, which are crucial for modulating treatment responses. Furthermore, we emphasize the promising synergy of immunotherapy with emerging treatments and the challenges and opportunities in refining these approaches to improve patient outcomes.