Tumor associated macrophage expressing <scp>CD</scp>204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma

<jats:p>Tumor associated macrophages (<jats:styled-content style="fixed-case">TAM</jats:styled-content>s) are the most abundant cancer stromal cells educated by tumor microenvironment to acquire trophic functions facilitating angiogenesis, matrix breakdown and cancer cell motility. Tumor associated macrophages have anti‐inflammatory properties or “alternatively” activated (<jats:styled-content style="fixed-case">M</jats:styled-content>2) phenotype expressing <jats:styled-content style="fixed-case">CD</jats:styled-content>204 and/or <jats:styled-content style="fixed-case">CD</jats:styled-content>163. To know the role of <jats:styled-content style="fixed-case">TAM</jats:styled-content>s in the growth and progression of esophageal squamous cell carcinomas (<jats:styled-content style="fixed-case">ESCC</jats:styled-content>s), we calculated intratumoral <jats:styled-content style="fixed-case">CD</jats:styled-content>204, <jats:styled-content style="fixed-case">CD</jats:styled-content>163 or <jats:styled-content style="fixed-case">CD</jats:styled-content>68 expressing macrophage count (<jats:styled-content style="fixed-case">M</jats:styled-content>ϕ<jats:styled-content style="fixed-case">C</jats:styled-content>) and <jats:styled-content style="fixed-case">CD</jats:styled-content>34‐positive microvessel density (<jats:styled-content style="fixed-case">MVD</jats:styled-content>) by immunohistochemistry in 70 cases of surgically resected <jats:styled-content style="fixed-case">ESCC</jats:styled-content>s and compared them with the clinicopathological factors and prognosis of patients. <jats:styled-content style="fixed-case">M</jats:styled-content>ϕ<jats:styled-content style="fixed-case">C</jats:styled-content> had positive linear association with <jats:styled-content style="fixed-case">MVD</jats:styled-content>. High <jats:styled-content style="fixed-case">CD</jats:styled-content>204<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">M</jats:styled-content>ϕ<jats:styled-content style="fixed-case">C</jats:styled-content> were significantly correlated with more malignant phenotypes including depth of tumor invasion, lymph and blood vessel invasion, lymph node metastasis as well as clinical stages. On the other hand, <jats:styled-content style="fixed-case">CD</jats:styled-content>163<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">M</jats:styled-content>ϕ<jats:styled-content style="fixed-case">C</jats:styled-content> did not associate with these clinicopathological factors with the exception of depth of tumor invasion and blood vessel invasion. Patients with high <jats:styled-content style="fixed-case">CD</jats:styled-content>204<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">M</jats:styled-content>ϕ<jats:styled-content style="fixed-case">C ESCC</jats:styled-content>s showed poor disease‐free survival (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>0.021). Conditioned media of five <jats:styled-content style="fixed-case">ESCC</jats:styled-content> cell lines (<jats:styled-content style="fixed-case">TE</jats:styled-content>‐8, ‐9, ‐10, ‐11 and ‐15) induced m<jats:styled-content style="fixed-case">RNA</jats:styled-content> as well as protein expression of <jats:styled-content style="fixed-case">CD</jats:styled-content>204 but not of <jats:styled-content style="fixed-case">CD</jats:styled-content>163 with upregulation of <jats:italic>vascular endothelial growth factor‐<jats:styled-content style="fixed-case">A</jats:styled-content></jats:italic> m<jats:styled-content style="fixed-case">RNA</jats:styled-content> in <jats:styled-content style="fixed-case">TPA</jats:styled-content> treated human acute monocytic leukemia cell line <jats:styled-content style="fixed-case">THP</jats:styled-content>‐1. These results overall indicate that <jats:styled-content style="fixed-case">CD</jats:styled-content>204 is a useful marker for <jats:styled-content style="fixed-case">TAM</jats:styled-content>s contributing to the angiogenesis, progression and prognosis of <jats:styled-content style="fixed-case">ESCC</jats:styled-content>s whose specific tumor microenvironment may educate macrophages to be <jats:styled-content style="fixed-case">CD</jats:styled-content>204<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">M</jats:styled-content>2 <jats:styled-content style="fixed-case">TAM</jats:styled-content>s.</jats:p>