This study investigates how HMGB1 compartmentalisation and O-GlcNAcylation regulate inflammatory signalling, autophagy, and immune escape in cancer. Our research focuses on HMGB1, a key mediator of inflammation and immune regulation. Because extracellular HMGB1 and related cytokines are detectable in blood, circulating plasma biomarkers may serve as systemic surrogates of tumour-immune microenvironment (TIME) biology.
Spatial profiling technologies-such as multiplex immunofluorescence (mIF) and GeoMx Digital Spatial Profiling (DSP)-enable precise mapping of HMGB1 localisation, O-GlcNAcylation status, and immune cell organisation within tumour tissues. Integrating these spatial tissue features with plasma cytokine signatures provides a mechanistic and clinically translatable approach for recurrence prediction. This study aims to determine whether baseline and early-on-treatment plasma cytokine profiles can predict recurrence in patients with esophageal squamous cell carcinoma (ESCC), and to evaluate how these circulating immune mediators correspond to spatially resolved TIME features.