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However, transient post-radiotherapy (RT) \u201cmetabolic flares\u201d 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 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.<\/jats:p>","DOI":"10.1093\/procel\/pwaf111","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T12:52:48Z","timestamp":1766062368000},"page":"631-643","source":"Crossref","is-referenced-by-count":3,"title":["ICAM-1 promotes T cell glycolytic reprogramming and tumor infiltration to drive 18F-FDG PET flares following radiotherapy"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3912-2175","authenticated-orcid":false,"given":"Rui","family":"Song","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Cancer Hospital and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University , Beijing 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Sciences, Peking University , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-0737","authenticated-orcid":false,"given":"Fuxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Peking University Third Hospital , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking University Third Hospital , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Cancer Hospital and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Cancer Hospital and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianze","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Cancer Hospital and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0927-721X","authenticated-orcid":false,"given":"Jinhong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Cancer Hospital and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Cancer Hospital and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191,","place":["China"]},{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Peking University Cancer Hospital , Beijing 100142,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Basic Medical Sciences, Peking University , Beijing 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