NEGAR TAGHAVI POURIANAZAR
Turkish Journal of Oncology - 2025;40(3):225-232
The unique tumor microenvironment (TME) of pancreatic cancer, one of the most deadly cancers, promotes immune evasion and immunosuppressive remodeling of the TME, contributing to tumor invasion, metastasis, and therapeutic resistance. Immune cells that play complex roles in this environment, often creating a highly immunosuppressive environment, include tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, dendritic cells (DCs), and B cells. The gut microbiota plays a crucial role in regulating the differentiation, activation, and function of these immune cells through metabolites such as short-chain fatty acids and signaling pathways like NF-κB and JAK-STAT. Dysbiosis, characterized by an imbalance in microbial populations, exacerbates immune suppression. It increases Tregs, MDSCs, and TAM polarization while decreasing CTL and NK cell activity. On the other hand, a balanced microbiome can enhance anti-tumor immunity, improving treatment efficacy and patient outcomes. This article provides a review of recent findings that highlight the complex relationships between immune cells and the microbiota in the pancreatic cancer TME, as well as the dual roles of these cells as both mediators of tumor progression and potential therapeutic targets. Novel approaches to treating pancreatic cancer are made possible by a promising strategy for reprogramming the immune microenvironment through modulation of the gut microbiota.
