Harnessing the effector-to-regulatory T cell ratio to advance prognosis and precision therapy in pancreatic cancer

Pancreatic cancer remains one of the most lethal malignancies, characterized by rapid progression, late-stage diagnosis, and resistance to current therapies. A major contributor to its poor prognosis is the highly immunosuppressive tumor microenvironment (TME), where regulatory T cells (Tregs) suppressing effector T cells (Teffs). The ratio of Teffs to Tregs (Teff/Treg ratio) has emerged as a pivotal biomarker that reflects immune balance within the TME, with significant prognostic and therapeutic relevance. A low Teff/Treg ratio correlates with poor clinical outcomes, immunotherapy resistance, and tumor progression. Elucidating the mechanisms regulating that regulate this ratio such as immune checkpoint pathways, cytokine-mediated signaling, and stromal interactions offers promising avenues to restore anti-tumor immunity. This review critically evaluates the prognostic values of the Teff/Treg ratio in pancreatic cancer, highlights emerging strategies to rebalance this axis, and outlines current challenges and research gaps. Standardizing measurement methodologies and integrating Teff/Treg analysis into pancreatic cancer-specific research are essential next steps toward precision immunotherapy.