Non-small cell lung cancer (NSCLC) is the leading cause of death by
cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC
tumor is a complex, heterogeneous microenvironment, comprising blood vessels,
cancer cells, immune cells, and stroma cells.
Vascular endothelial growth factors (
VEGFs) are a major mediator to induce
tumor microvasculature and are associated with the progression, recurrence, and
metastasis of NSCLC. Current treatment medicines targeting
VEGF/
VEGF receptor (VEGFR) pathway, including
neutralizing antibodies to
VEGF or VEGFR and
receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC.
VEGF is not only an important
angiogenic factor but also an
immunomodulator of tumor microenvironment (TME).
VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of
VEGF in NSCLC, especially the interaction between
VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore
VEGF/VEGFR-targeted compounds and
immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.