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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Esophageal squamous cell carcinoma; Intratumoral microbiota; Lipopolysaccharide; Tumor microenvironment; Tumor-associated macrophage.