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

Burmeister, Katharina and Quagliata, Luca and Andreozzi, Mariacarla and Eppenberger-Castori, Serenella and Matter, Matthias S. and Perrina, Valeria and Grobholz, Rainer and Jochum, Wolfram and Horber, Daniel and Moosmann, Peter and Lehmann, Frank and Köberle, Dieter and Ng, Charlotte K. Y. and Piscuoglio, Salvatore and Tornillo, Luigi and Terracciano, Luigi M.. (2017) 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, 12 (4). e0175563.

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Piscuoglio, Salvatore
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public liberary of science
ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:25 Jan 2019 14:07
Deposited On:25 Jan 2019 14:07

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