Regulatory T Cells Along the Pancreatitis-Pancreatic Cancer Continuum: Context-Dependent Immune Control and Therapeutic Opportunities.

Regulatory T cells (Tregs) are essential for maintaining immune tolerance and limiting collateral tissue injury during inflammation. In pancreatic diseases, however, Treg function is highly context-dependent: protective in acute inflammatory settings by restraining excessive immune activation, yet potentially pathogenic by fostering immunosuppression and immune escape in pancreatic ductal adenocarcinoma (PDAC). Acute pancreatitis (AP), chronic pancreatitis (CP), and PDAC share overlapping immune microenvironmental features, including cytokine-driven T-cell reprogramming, barrier dysfunction-associated microbial translocation, and stromal-immune crosstalk. Understanding Treg behaviour along the pancreatitis-PDAC continuum requires deciphering context-dependent immune microenvironmental mechanisms that shift from protective regulation to tumour-promoting immunosuppression. Recent evidence highlights that indiscriminate Treg depletion may paradoxically accelerate pancreatic tumorigenesis in specific settings, underscoring the need to resolve Treg heterogeneity, tissue residency, and stage-specific roles. In this review, we summarise current mechanistic insights into Treg-mediated regulation in AP and CP (including Th17/Treg balance and fibrosis-associated immune networks) and in PDAC (including Treg phenotypic diversity and interactions with myeloid cells and stroma). We further discuss emerging therapeutic strategies that modulate Tregs directly or indirectly, and propose a translational framework for aligning Treg-targeted interventions with disease stage and immune context to improve outcomes in pancreatic inflammation and cancer.