The Local Microbiome in Esophageal Cancer and Treatment Response: A Review of Emerging Data and Future Directions

Simple Summary Esophageal and esophagogastric junction cancers are not well explained by traditional risk factors and have high mortality rates and limited treatment options. The aim of this review article is to describe the potential role of the local tumor microbiome in upper GI carcinogenesis, as well as treatment responses, and to further describe the challenges and opportunities in conducting and interpreting high-quality microbiome studies. Immunotherapy is now approved for clinical use, and several lessons from studies of the gut microbiome's role in immune checkpoint inhibitor responses in melanoma, lung, and genitourinary cancers may also inform esophageal cancer studies. The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and the cancer treatment response. The advent of nucleic acid sequencing technologies has enabled more comprehensive, culture-independent bacterial identification. Across several tumor types, studies of tissue-specific microbiomes have shown associations between the overall microbiome composition, the relative abundance of specific bacteria, and tumorigenesis. Furthermore, in the era of cancer immunotherapy, several studies have demonstrated that the microbiome and specific bacteria may modify treatment responses and the risk of immune-related adverse events. Design: peer-reviewed, published studies describing the role of local, gastrointestinal-specific microbiota or the role of the gut microbiome in treatment responses were reviewed. PubMed was searched from 1 September 2022 to 1 November 2022, using the following terms in combination: "microbiome", "tumor microbiome", "esophageal cancer", "cancer", "cancer treatment", and "immunotherapy". Original research articles were considered, and other reviews or editorials were discarded. In total, approximately 250 articles were considered. Results: over 70 studies describing microbiome research in either gastrointestinal carcinogenesis or the systemic treatment response were identified and reviewed. Conclusions: a growing body of evidence supports the role of the esophageal microbiome in both esophageal tumorigenesis and the immune checkpoint inhibitor response. More well-designed, comprehensive studies are required to collect the appropriate clinical, microbial, and immunophenotype data that are needed to clarify the precise role of the microbiome in esophageal carcinogenesis and treatment.