Intratumoral Lipopolysaccharide Positivity Related to Tumor-Associated Macrophage Infiltration and Poor Prognosis in Esophageal Squamous Cell Carcinoma.

Abstract

Prognosis in esophageal squamous cell carcinoma (ESCC) is influenced by the tumor microenvironment, where CD163-positive M2-like tumor-associated macrophages promote immune suppression and tumor progression. Lipopolysaccharide (LPS), markers of intratumoral microbiota, activate nuclear factor-kappa B (NF-κB) signaling and inflammation. Inflammation-based prognostic scores, such as the lymphocyte-to-monocyte ratio (LMR), are poor prognostic factors in various types of cancers. This study evaluated the impact of intratumoral LPS on systemic inflammation and the tumor microenvironment in ESCC. Surgical specimens from 134 patients with ESCC were analyzed. Immunohistochemical staining was performed to evaluate intratumoral LPS positivity and its associations with clinicopathological factors, prognosis, inflammation-based prognostic scores, including LMR, CD163-positive TAM infiltration, and nuclear NF-κB expression, and tumoral vimentin expression as an epithelial-mesenchymal transition/mesenchymal marker in patients with ESCC. LPS was identified in ESCC cell nuclei and cytoplasm. High intratumoral LPS positivity was associated with N factor progression, high NF-κB nuclear positivity, low LMR, and high stromal CD163-positive TAM infiltration, and it served as an independent poor prognostic factor. Lipopolysaccharide positivity was significantly related to poor prognosis in CD163-positive TAM cases, compared with LPS negativity. Detection of LPS in resected ESCC tissues could be a reliable biomarker for identifying high-risk patients with aggressive tumor characteristics, systemic inflammation, and impaired tumor immunity.