Burmeister Katharina, Quagliata Luca, Andreozzi Mariacarla, Eppenberger-Castori Serenella, Matter Matthias S, Perrina Valeria, Grobholz Rainer, Jochum Wolfram, Horber Daniel, Moosmann Peter, Lehmann Frank, Köberle Dieter, Ng Charlotte K Y, Piscuoglio Salvatore, Tornillo Luigi, Terracciano Luigi M
Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, Basel, Switzerland.
Institute of Pathology, Cantonal Hospital Aarau, Tellstrasse 25, Aarau, Switzerland.
PLoS One. 2017 Apr 12;12(4):e0175563. doi: 10.1371/journal.pone.0175563. eCollection 2017.
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.
血管内皮生长因子A（VEGFA）是一种由肿瘤分泌的血管生成因子，特别是那些具有VEGFA扩增的肿瘤，以及肿瘤微环境中的巨噬细胞和淋巴细胞。在这里，我们试图确定在携带VEGFA扩增或6号染色体多倍体的结直肠癌中M1/M2巨噬细胞、PD-1阳性淋巴细胞以及肿瘤和基质中PD-L1表达的情况。通过免疫组织化学法对38例结直肠癌进行评估，其中13例携带VEGFA扩增，6例有6号染色体多倍体，19例VEGFA拷贝数为中性，检测指标包括CD68（M1/M2巨噬细胞标志物）、CD163（M2巨噬细胞）、程序性死亡蛋白1（PD-1）——肿瘤浸润及基质淋巴细胞，以及肿瘤和基质中PD-1配体（PD-L1）的表达。携带VEGFA扩增或6号染色体多倍体的结直肠癌与M1/M2巨噬细胞减少、表达PD-1的淋巴细胞浸润减少以及肿瘤前沿基质中PD-L1表达降低有关。与中分化结直肠癌相比，高分化结直肠癌与M1/M2巨噬细胞增加以及肿瘤中PD-L1表达增加有关。我们的结果表明，VEGFA扩增或6号染色体多倍体与肿瘤免疫微环境改变有关。
