Purpose: Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear. Experimental Design: We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum–positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data. Results: Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22–3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06–2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum–positive tissues was “cytokine–cytokine receptor interaction.” A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC. Conclusions: F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574–81. ©2016 AACR.

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.

Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD‐1) or programmed death‐ligand 1 (PD‐L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD‐L1 expression on tumors, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.

BACKGROUND: The prognostic nutritional index is reportedly related to postoperative outcomes. OBJECTIVE: The aim of this study was to elucidate the clinical importance of the prognostic nutritional index in patients with colorectal cancer who were undergoing primary tumor resection. DESIGN: This is a retrospective study from a single institution. SETTINGS: This study was conducted at a colorectal surgery service in an academic teaching hospital. PATIENTS: The 556 patients with colorectal cancer who were undergoing surgery between March 2005 and August 2014 were eligible for this study. MAIN OUTCOME MEASURES: The preoperative prognostic nutritional index was calculated. Classification and regression tree analysis was performed to determine the prognostic nutritional index cutoff value. The associations of the prognostic nutritional index status with clinicopathological factors and postoperative outcomes were examined using univariate and multivariate analyses. RESULTS: Classification and regression tree analysis demonstrated that 45.5 was the optimal cutoff value. The low status (≤45.5) was correlated with older age, low BMI, low estimated glomerular filtration rate, CEA positivity, carbohydrate antigen 19-9 positivity, preoperative chemotherapy, tumors invading muscular or deeper layers, distant metastasis, poor differentiation, severe postoperative complications, tumor recurrence, and poor survival. In multivariate analysis, the low status was an independent risk factor for severe postoperative complications (OR = 2.06 [95% CI, 1.22–3.50]; p = 0.007) and low overall survival (HR =3.98 [95% CI, 2.38–6.89]; p < 0.001). LIMITATIONS: Our data set was collected retrospectively from a single institution. In addition, our study was only for preoperative prognostic nutritional index status, not considering the postoperative host status. CONCLUSIONS: The preoperative prognostic nutritional index predicts severe complications, recurrence, and poor prognosis in patients with colorectal cancer who are undergoing primary tumor resection. Investigation of the nutritional and immunologic statuses using the prognostic nutritional index could be a useful clinical approach.