The Relationship Between Gut Microbiome Bifidobacterium and Anti-tumor Immune Responses in Esophageal Squamous Cell Carcinoma.

Abstract

The Bifidobacterium genus is a prominent bacterial population in the gastrointestinal tract. Previous findings suggest that Bifidobacterium is linked to tumor suppression in mouse models of melanoma. Additionally, when combined with the programmed death-ligand 1 (PD-L1) antibody, it can enhance anti-tumor treatment by increasing tumor-specific T-cell responses and promoting infiltration of antigen-specific T cells into tumors. However, there is a lack of studies on Bifidobacterium in esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the potential impact of Bifidobacterium on this cancer type. We examined 213 samples from ESCC patients who underwent tumor resection. The presence of Bifidobacterium was confirmed using quantitative polymerase chain reaction and fluorescent in situ hybridization (FISH). Patient overall survival (OS) was analyzed with Bifidobacterium positivity. Tumor-infiltrating lymphocytes (TILs) were evaluated via hematoxylin and eosin stains, and immunohistochemistry was used to assess programmed death-1 (PD-1), PD-L1, cluster of differentiation 8 (CD8), and forkhead box P3 (FOXP3) expression. Nutritional status was evaluated via computed tomography scans. Bifidobacterium positivity showed no correlation with patient OS or TIL levels; however, Bifidobacterium positivity in normal tissue was associated with lower FOXP3 levels, suggesting a potential role in upregulating anti-tumor immune responses. Patients with Bifidobacterium present in peritumor normal tissue exhibited better skeletal muscle area and volume. Conversely, Bifidobacterium positivity in tumor tissue was associated with poorer prognostic nutrition index values, likely due to decreased albumin levels. Bifidobacterium can induce the upregulated anti-tumor immune response and is more prevalent in cases with good nutritional status.