Radiotherapy (RT) is one of the most widely used cancer treatment modalities, applied in over half of all patients with cancer. In clinical oncology, positron emission tomography (PET) with 18 F-fluorodeoxyglucose ( 18 F-FDG) is widely used to noninvasively monitor tumor glucose metabolism and evaluate therapeutic responses, including those to RT. However, transient increases in 18 F-FDG uptake—referred to as post-RT “metabolic flares”—are frequently observed in responding tumors and have traditionally been attributed to localized inflammatory reactions. Whether these flares reflect underlying immune cell dynamics, particularly tumor-infiltrating T cells, has remained poorly understood.
In this study, through integrated analyses of patient samples and multiple mouse tumor models, RT was shown to robustly induce intracellular adhesion molecule-1 (ICAM-1) expression within tumors and to promote T cell infiltration. Genetic ablation of ICAM-1 markedly attenuated RT-induced 18 F-FDG flares, an effect primarily attributable to reduced glucose uptake and tumor infiltration of T cells rather than myeloid cells. Mechanistically, RT-induced ICAM-1 engages lymphocyte function-associated antigen-1 (LFA-1) to facilitate T cell clustering and intratumoral accumulation, thereby activating the PI3K–AKT–mTOR signaling pathway and driving metabolic reprogramming characterized by enhanced glycolysis and tricarboxylic acid (TCA) cycle activity.
This study establishes ICAM-1 as a key regulator of T cell metabolic reprogramming and tumor infiltration following RT. These findings offer a mechanistic framework for more accurate interpretation of post-RT PET imaging, support the use of ICAM-1 as a biomarker to distinguish pseudoprogression from true tumor progression, and provide new avenues for monitoring antitumor immune dynamics and optimizing RT-based combination therapies.
Radiotherapy-induced ICAM-1 upregulation promotes T cell clustering through ICAM-1–LFA-1 interactions, activates PI3K–AKT–mTOR signaling, and thereby drives T cell glycolytic reprogramming and tumor infiltration, leading to 18 F-FDG PET flares
Protein & Cell
Experimental study
Not applicable
ICAM-1 promotes T cell glycolytic reprogramming and tumor infiltration to drive 18F-FDG PET flares following radiotherapy
19-Dec-2025