Microbiome as a modulator of immunotherapy response in pancreatic cancer

Pancreatic adenocarcinoma is widely regarded as one of the most lethal malignancies due to its rapid progression and the limited success of early detection methods and therapeutic interventions. While immunotherapy has emerged as an effective treatment option for various solid tumors, it has not demonstrated comparable efficacy in pancreatic cancer. Further research is required to evaluate the safety and efficacy of different immunotherapy modalities, including immune checkpoint inhibitors, T-cell transfer therapy, chimeric antigen receptor T-cell therapy, neoantigen vaccines, and epigenome-targeting treatments, specifically in the context of pancreatic cancer. Emerging evidence highlights the crucial role of the microbiome in modulating cancer cells’ responses to immunotherapy. Studies have increasingly implicated the gut microbiota composition as a direct influencer of tumorigenesis in pancreatic cancer. Certain microbial species have been shown to exert immunostimulatory or immunosuppressive effects on pancreatic cancer cells, thereby directly enhancing or suppressing their response to immunotherapeutic regimens. Despite these findings, there remains a paucity of comprehensive reviews on microbiome studies specific to individual immunotherapy modalities in pancreatic cancer. This review highlights the exciting potential of the microbiome in modulating pancreatic cancer responses across various immunotherapy subtypes and emphasizes the clinical need for further research in the field.