Objective: To determine whether prognostic nutritional index (PNI) affects clinical outcome through local immunity in esophageal cancers. Background: PNI is an indicator of nutritional status and systemic immune competence, and has attracted attention as a prognostic biomarker. Tumor-infiltrating lymphocytes (TILs) are a specific histological feature of human cancers, reflecting an individual's immunological tumor response. Methods: Using a nonbiased database of 337 curatively resected esophageal cancers, we evaluated the relationship between PNI, TILs status, CD8 expression by immunohistochemical staining, and clinical outcome. Results: Compared with PNI-high cases (n = 220), PNI-low cases (n = 117) showed significantly worse overall survival (log-rank P < 0.001; hazard ratio: 2.23; 95% confidence interval: 1.56–3.18; P < 0.001; multivariate hazard ratio: 1.67; 95% confidence interval: 1.14–2.44; P = 0.008). The TILs status was also significantly correlated with overall survival (P < 0.001). In addition, PNI was significantly associated with TILs status (P < 0.001) and the CD8-positive cell count (P = 0.041). A significant relationship between the peripheral blood lymphocyte count and TILs status was also observed (P < 0.001). Conclusions: PNI and TILs score expression were associated with clinical outcome in esophageal cancer, supporting their roles as prognostic biomarkers. Considering the relationship between PNI and TILs, nutritional status and systemic immune competence may influence patient prognosis through local immune response.

PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. In addition, the combination with TIL status enabled further classification patients according to clinical outcome. PD-L1 expression and TIL status may serve as predictive tissue biomarkers and can be used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1 pathways.

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IDO1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. Combining the IDO1 and CD8 statuses enabled further classification of the clinical outcomes of patients.

Epigenetic changes play a crucial role in human cancer development. DNA methylation is a central epigenetic process that regulates levels of gene expression. Changes in DNA methylation that occur in human tumors include global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Long interspersed element-1 (LINE-1) is a repetitive DNA retrotransposon that duplicates via a copy-and-paste genetic mechanism. As LINE-1 constitutes approximately 17% of the human genome, the extent of LINE-1 methylation is regarded as a surrogate marker of global DNA methylation. In a variety of gastrointestinal (GI) cancers, LINE-1 hypomethylation is strongly associated with a poor prognosis, supporting its potential role as a prognostic biomarker. In this article, we summarize current knowledge regarding LINE-1 methylation and its prognostic impact in GI cancers.