Brown adipose tissue activation and cardiovascular risk following PD-1 antibody therapy in cancer patients: a retrospective cohort study.

BACKGROUND: This study aimed to investigate whether PD-1 antibody therapy modulates brown adipose tissue (BAT) activity and whether BAT activation is associated with cardiovascular risk parameters in cancer patients. METHODS DESIGN: Retrospective cohort study. SETTING: Two tertiary hospitals in Fujian Province, China (Fujian Provincial Hospital and Fujian Cancer Hospital), between January 2019 and January 2024. PARTICIPANTS: Sixty-eight cancer patients (54 males, 14 females) who received PD-1 antibody therapy (e.g., pembrolizumab, 200 mg Q3W) and underwent paired 18F-FDG PET/CT scans (pre-treatment and post-treatment, median interval: 3.2 months). EXCLUSION CRITERIA: hypothyroidism (n = 3), severe renal insufficiency (n = 2), and incomplete PET/CT or laboratory data. OUTCOME MEASURES: primary outcome: change in BAT activity (quantified by supraclavicular fossa SUVmax via PET/CT) pre- versus post-PD-1 therapy. SECONDARY OUTCOMES: changes in VAT/SAT SUVmax, lipid profiles (triglycerides [TG], total cholesterol [TC], LDL-C, and HDL-C), arterial stiffness index (ASI), cardiac biomarkers (cTnT and NT-proBNP), and thyroid function (TSH, FT3, FT4). RESULTS: Following immunotherapy, BAT SUVmax exhibited a marked increase of 68.0%, whereas visceral and subcutaneous fat SUVmax rose by 29.6% and 30.8%, respectively (P < 0.001 for all). Significant dyslipidemia was observed post-treatment (P < 0.05): arterial stiffness index (ASI) increased by 17.0%, triglycerides by 22.6%, total cholesterol by 9.6%, and LDL-C by 9.7%. Notably, partial correlation analysis revealed an inverse relationship between BAT activity and ASI (r = - 0.321, P = 0.011). Multivariate linear regression identified ASI (β = - 1.208, P = 0.009) and high-density lipoprotein (β = - 1.074, P = 0.038) as independent predictors of BAT activity. CONCLUSIONS: PD-1 antibodies enhance BAT activity in cancer patients, and higher BAT activity is associated with reduced arterial stiffness. PET/CT-derived BAT SUVmax may serve as a novel biomarker for cardiovascular risk stratification during PD-1 antibody therapy.