Co‐Infection by Porphyromonas gingivalis and Fusobacterium nucleatum Increases PD‐L1 Expression in Esophageal Cancer Tissues

Currently, the impact of the microbiome on the progression and recurrence of esophageal cancer remains unclear. Microbes have been demonstrated to increase programmed death‐ligand 1 (PD‐L1) expression in certain epithelial tumors, thereby facilitating immune escape. Therefore, we hypothesized that the microbiome in esophageal tissues might be involved in the progression and recurrence of esophageal squamous cell carcinoma (ESCC) through PD‐L1 upregulation. To assess this possibility, we analyzed the relationship between the microbial community composition and PD‐L1 expression. We found that the microbiome of esophageal cancer tissue significantly differs from that of normal tissue, and Porphyromonas gingivalis and Fusobacterium nucleatum could represent markers of ESCC. An immunohistochemical assay revealed that P. gingivalis and F. nucleatum infection led to a significant increase in PD‐L1 expression on the membrane surface of tumor cells, and this finding was further confirmed in cell experiments. Our findings suggest that eliminating intratumoral P. gingivalis and F. nucleatum infection could represent an important therapeutic strategy for reducing the progression and recurrence of esophageal cancer.