The Emerging Role of the c-MET-HGF Axis in Non-small Cell Lung Cancer Tumor Immunology and Immunotherapy

Abstract

Study of the c-Met-HGF axis in non-small cell lung cancer (NSCLC) has focused on the roles of c-MET signaling in neoplastic epithelial cells and the secretion of its ligand hepatocyte growth factor (HGF) by tumor stromal cells. However, there is increasing evidence that some leukocyte subsets also express c-MET raising the possibility of an immunomodulatory role for this axis. Consequently, the role of the c-MET-HGF axis in immunoncology is an active area of ongoing research. This review summarizes current knowledge of c-MET expression in NSCLC, the prognostic significance of these findings and the mechanisms by which the c-MET-HGF axis might act in NSCLC, focusing on the emerging evidence for an immunoregulatory role.

Plasma Biomarkers Screening by Multiplex ELISA Assay in Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

“…Also, it is established that HGF induces macrophage transition to the M2 phenotype, which is pro-generative. However, several studies have suggested that HGF could also have a pro-immune role [36,37] and further research is needed to better understand the exact role of HGF in anti-tumour immune response.…”

Crizotinib in Patients With MET-Amplified NSCLC

“…MET amplification has been reported as a rare, potentially actionable, primary oncogenic driver in a subset of patients with NSCLC, with frequency depending on the definition used. 1 This is separate from its role as an acquired resistance pathway to tyrosine kinase inhibitors (TKIs) in NSCLC 2,3 or as a concurrent alteration within patients with MET exon 14 with NSCLC. 4,5 In patients with MET exon 14-altered NSCLC, reported objective responses to MET inhibition do not seem to be influenced by the absence, presence, or levels of concurrent MET amplification.…”

Co-stimulatory and co-inhibitory Immune Markers in Solid Tumors With MET Alterations

“…Previous studies have shown that the nCounter technique can accurately analyze mRNA from formalin-fixed, paraffin-embedded (FFPE) tissue, with results similar to fresh frozen tissue [ 18 , 19 ]. MET receptor tyrosine kinase alterations have previously been shown to correlate with expression of immunoregulatory molecules, including PD-L1, and may play a role in immune evasion [ 20 , 21 ]. Therefore, this study was conducted to investigate the expression of immune markers in solid tumors with MET alterations to identify markers that may be associated with tumorigenesis.…”