RGF (Ready–Go–Fever) in Cholangiocarcinoma: A Spatiotemporal Immune Synchronization Framework for Biliary Intervention–Associated Anti-Tumour Immunity

A Spatiotemporal Intervention Strategy Addressing the Limitations of SAAT in Biliary Tumour Immunity** Cholangiocarcinoma and related biliary tract malignancies remain among the most immunotherapy-resistant solid tumours, despite advances in immune checkpoint blockade and locoregional interventions. Emerging evidence suggests that therapeutic failure is not solely attributable to insufficient immune activation, but may reflect a deeper spatiotemporal limitation in antigen accessibility and adaptive immune coordination. The Spatiotemporal Antigen Accessibility Theory (SAAT) proposes that in biliary tract tumours, immune escape arises from a mismatch between antigen availability and adaptive immune readiness. Contributing factors may include delayed or insufficient lymphatic activation, functional impairment of tumour-draining lymph nodes, and spatial barriers that restrict effective dendritic-cell priming and T-cell maturation. As a result, even when tumour antigens are released through ablation or inflammation, they may occur outside an effective immune “readiness window,” leading to incomplete or inefficient systemic immune responses. To address these limitations, we propose the RGF (Ready–Go–Fever) framework as a staged interventional strategy derived from SAAT. The RGF model aims to restore temporal coordination between lymphatic priming and antigen release through sequential intervention.