Vascular endothelial growth factor A amplification in colorectal cancer is associated with reduced M1 and M2 macrophages and diminished PD-1-expressing lymphocytes

<div><p>VEGFA is an angiogenic factor secreted by tumors, in particular those with <i>VEGFA</i> amplification, as well as by macrophages and lymphocytes in the tumor microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD-1-positive lymphocytes and PD-L1 tumoral and stromal expression in colorectal cancers harboring <i>VEGFA</i> amplification or chromosome 6 polysomy. 38 CRCs of which 13 harbored <i>VEGFA</i> amplification, 6 with Chr6 polysomy and 19 with neutral <i>VEGFA</i> copy number were assessed by immunohistochemistry for CD68 (marker for M1/M2 macrophages), CD163 (M2 macrophages), programmed death 1(PD-1)- tumor infiltrating and stromal lymphocytes as well as tumoral and stromal PD-1 ligand (PD-L1) expression. CRCs with <i>VEGFA</i> amplification or Chr6 polysomy were associated with decreased M1/M2 macrophages, reduced PD-1-expressing lymphocyte infiltration, as well as reduced stromal expression of PD-L1 at the tumor front. Compared to intermediate-grade CRCs, high-grade CRCs were associated with increased M1/M2 macrophages and increased tumoral expression of PD-L1. Our results suggest that <i>VEGFA</i> amplification or Chr6 polysomy is associated with an altered tumor immune microenvironment.</p></div