title: Vascular endothelial growth factor A amplification in colorectal cancer is associated with reduced M1 and M2 macrophages and diminished PD-1-expressing lymphocytes.
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.
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Burmeister
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Quagliata
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Andreozzi
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Serenella
authors.initials: S
authors.lastname: Eppenberger-Castori
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Matter
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Valeria
authors.initials: V
authors.lastname: Perrina
authors.affiliation: Institute of Pathology, Cantonal Hospital Aarau, Tellstrasse 25, Aarau, Switzerland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Grobholz
authors.affiliation: Institute of Pathology, Cantonal Hospital St. Gallen, Rorschacher Strasse 95, St. Gallen, Switzerland.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.affiliation: Medical Oncology and Hematology, Cantonal Hospital St. Gallen, Rorschacher Strasse 95, St. Gallen, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Horber
authors.affiliation: Medical Oncology, Cantonal Hospital Aarau, Tellstrasse 25, Aarau, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Moosmann
authors.affiliation: Division of Gastroenterology, University Hospital of Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Lehmann
authors.affiliation: Medical Oncology, St. Claraspital, Kleinriehenstrasse 30, Basel, Switzerland.
authors.forename: Dieter
authors.initials: D
authors.lastname: Köberle
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Charlotte K Y
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Salvatore
authors.identifier: http://orcid.org/0000-0003-2686-2939
authors.initials: S
authors.lastname: Piscuoglio
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.|GILab AG, Lettenweg 118, Allschwil, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D056726:Genetic Association Studies; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A