Journal Article

ICAM-1 promotes T cell glycolytic reprogramming and tumor infiltration to drive 18F-FDG PET flares following radiotherapy

Zhao, Meixin, Song, Rui, Zhang, Ting, Zhang, Weifang, He, Huiying, Li, Kui, Zhu, Hua, Wang, Feng, Yang, Zhi, Zhou, Shixin, Zhang, Yining, Liu, Zhaofei, Zhou, Haoyi, Wang, Jianze, Du, Jinhong, Guo, Fuxin, Wang, Jiadong

2025

Overview

18F-fluorodeoxyglucose (18F-FDG) is the most widely used radiotracer for positron emission tomography (PET) imaging in clinical oncology, owing to the elevated glycolytic activity of tumor cells. However, transient post-radiotherapy (RT) “metabolic flares” of 18F-FDG uptake are frequently observed in patients and are traditionally attributed to localized inflammatory responses. Whether these flares are linked to immune cell dynamics, particularly tumor-infiltrating T cells, and the mechanisms involved remain poorly understood. Here, we demonstrate that RT markedly upregulates intracellular adhesion molecule-1 (ICAM-1) expression and promotes T cell infiltration in tumors, as observed in both patients and mouse models. Genetic ablation of ICAM-1 significantly attenuates RT-induced metabolic flares in irradiated tumors, primarily due to reduced 18F-FDG uptake by tumor-infiltrating T cells rather than myeloid cells. Mechanistically, ICAM-1 engages with lymphocyte function-associated antigen 1 (LFA-1) to facilitate T cell clustering, thereby promoting their intratumoral accumulation and activating glycolysis and the tricarboxylic acid (TCA) cycle via the PI3K-AKT-mTOR signaling pathway. These findings identify ICAM-1 as a critical regulator of T cell metabolic reprogramming and tumor infiltration following RT, offering a mechanistic explanation for 18F-FDG PET flares. Clinical monitoring of post-RT tumor ICAM-1 expression may enhance PET interpretation and aid in distinguishing pseudoprogression from true tumor progression.