Video Experimental Relacionado
Updated: Feb 17, 2026
Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
Oxidación de Ácidos Grasos mediada por CD36 en CTCs impulsa la Evasión Inmune y la Metástasis en CPNM
Huizhen Zhu1,2, Shuiyan Dai3, Fengping Wang2
1School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China.
Background:
Immune checkpoint inhibitors (ICIs) show clinical benefit in subsets of non-small cell lung cancer (NSCLC) patients, yet resistance remains a major challenge. Circulating tumor cells (CTCs) contribute to tumor dissemination and immune regulation. This study investigated the metabolic features of CTC subpopulations under PD-1 resistance, with a focus on the role of CD36+CTCs in immune evasion and pre-metastatic niche (PMN) formation.
Methods:
PD-1-resistant in vitro and murine NSCLC models were established to enrich and isolate CTCs. CD36+ CTCs were characterized using lipid metabolomics, RNA sequencing, and functional assays. Their roles in PMN formation and immune suppression were evaluated using lung metastasis models and a tri-cell co-culture system. Fatty acid oxidation (FAO) dependency was assessed by lipid imaging, mitochondrial activity analysis, and pharmacological inhibition with etomoxir.
Results:
CD36+ CTCs were enriched under PD-1 resistance and exhibited enhanced lipid accumulation, increased mitochondrial activity, and FAO dependency. Multi-omics analyses revealed activation of lipid metabolic pathways associated with immune suppression and extracellular matrix remodeling. Functionally, CD36+ CTCs promoted PMN formation and inhibited T-cell activation, while FAO inhibition significantly reduced their migratory and metastatic potential.
Conclusion:
CD36+ CTCs drive immune evasion and metastasis in PD-1-resistant NSCLC through FAO-dependent metabolic reprogramming. Targeting this metabolic vulnerability may enhance the efficacy of immunotherapy.
