The Influence of the Microbiome on Immunotherapy for Gastroesophageal Cancer

Abstract

Immunotherapy has shown promise as a treatment option for gastroesophageal cancer, but its effectiveness is limited in many patients due to the immunosuppressive tumor microenvironment (TME) commonly found in gastrointestinal tumors. This paper explores the impact of the microbiome on the TME and immunotherapy outcomes in gastroesophageal cancer. The microbiome, comprising microorganisms within the gastrointestinal tract, as well as within malignant tissue, plays a crucial role in modulating immune responses and tumor development. Dysbiosis and reduced microbial diversity are associated with poor response rates and treatment resistance, while specific microbial profiles correlate with improved outcomes. Understanding the complex interactions between the microbiome, tumor biology, and immunotherapy is crucial for developing targeted interventions. Microbiome-based biomarkers may enable personalized treatment approaches and prediction of patient response. Interventions targeting the microbiome, such as microbiota-based therapeutics and dietary modifications, offer the potential for reshaping the gut microbiota and creating a favorable TME that enhances immunotherapy efficacy. Further research is needed to reveal the underlying mechanisms, and large-scale clinical trials will be required to validate the efficacy of microbiome-targeted interventions.

Keywords: PD1 blockade; biomarkers; gastroesophageal cancers; immunotherapy; microbiome; prognosis; resistance; survival.

Figure 1

The figure illustrates the microbiome composition at different body sites, including the oral cavity, gastric region, gut, and tumor. It highlights the associations between the microbiome and esophageal cancer and gastric cancer, indicating increases or decreases in specific bacteria. The analysis is conducted at the genus level, representing groups of related bacteria.

Figure 2

The figure illustrates the impact of the microbiome on cancer hallmarks and tumor biology. It highlights the specific effects of bacteria on various aspects of cancer progression, including sustained proliferating signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing vasculature, activating invasion and metastasis, deregulating cellular metabolism, avoiding immune destruction, promoting tumor-promoting inflammation, genome instability and mutation, reprogramming cellular signaling, unlocking phenotypic plasticity, non-mutational epigenetic reprogramming, and polymorphic microbiomes. Detailed explanations of these effects are provided in the body of the article.