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

Publication

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

Journal Paper/Review - Apr 12, 2017

Burmeister Katharina, Tornillo Luigi, Piscuoglio Salvatore, Ng Charlotte K Y, Köberle Dieter, Lehmann Frank, Moosmann Peter, Horber Daniel, Jochum Wolfram, Grobholz Rainer, Perrina Valeria, Matter Matthias S, Eppenberger-Castori Serenella, Andreozzi Mariacarla, Quagliata Luca, Terracciano Luigi M

Citation

Burmeister K, Tornillo L, Piscuoglio S, Ng C, Köberle D, Lehmann F, Moosmann P, Horber D, Jochum W, Grobholz R, Perrina V, Matter M, Eppenberger-Castori S, Andreozzi M, Quagliata L, Terracciano L. Vascular endothelial growth factor A amplification in colorectal cancer is associated with reduced M1 and M2 macrophages and diminished PD-1-expressing lymphocytes. PloS one 2017; 12:e0175563.

Type

Journal Paper/Review (English)

Journal

PloS one 2017; 12

Publication Date

Apr 12, 2017

Issn Electronic

1932-6203

Pages

e0175563

Brief description/objective

VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA 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 VEGFA amplification or chromosome 6 polysomy. 38 CRCs of which 13 harbored VEGFA amplification, 6 with Chr6 polysomy and 19 with neutral VEGFA 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 VEGFA 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 VEGFA amplification or Chr6 polysomy is associated with an altered tumor immune microenvironment.