Recently approved and highly specific small-molecule inhibitors of c-MET exon 14 
skipping mutations (e.g., capmatinib, tepotinib) are a new and important 
therapeutic option for the treatment of non-small cell lung cancer (NSCLC) 
patients harbouring c-MET alterations. Several experimental studies have 
provided compelling evidence that c-MET is involved in the regulation of the 
immune response by up-regulating inhibitory molecules (e.g., PD-L1) and 
down-regulating of immune stimulators (e.g., CD137, CD252, CD70, etc.). In 
addition, c-MET was found to be implicated in the regulation of the inflamed 
tumour microenvironment (TME) and thereby contributing to an increased immune 
escape of tumour cells from T cell killing. Moreover, it is a major resistance 
mechanism following treatment of epidermal growth factor receptor mutations 
(EGFRmut) with tyrosine kinase receptor inhibitors (TKIs). In line with these 
findings c-MET alterations have also been shown to be associated with a worse 
clinical outcome and a poorer prognosis in NSCLC patients. However, the 
underlying mechanisms for these experimental observations are neither fully 
evaluated nor conclusive, but clearly multifactorial and most likely 
tumour-specific. In this regard the clinical efficacy of checkpoint inhibitors 
(CPIs) and TKIs against EGFRmut in NSCLC patients harbouring c-MET alterations 
is also not yet established, and further research will certainly provide some 
guidance as to optimally utilise CPIs and c-MET inhibitors in the future.