2026-10-13T18:31:08Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33770596 2026-09-15T04:24:19Z category_696 portal_316 item_type_3 month_year_09_2026

Data Sheet 1_Cancer stem cell programs S-nitrosylation and deubiquitination of FoxP3 protein to promote regulatory T cell differentiation.pdf Xiyu Liu (1700959) Jiaxin Lei (143514) Xinhang Jiang (182904) Lingyi Li (6819935) Longhao Yu (24911848) Gengxue Wang (24911851) Kaixun Guo (24911854) Zhenke Wen (219096) Yan Wang (15435) Genetic Immunology CSCs deubiquitination Foxp3 regulatory T cell S-nitrosylation Background<p>Cancer stem cells (CSCs) are critical drivers of tumor progression and therapeutic resistance in non-small cell lung cancer (NSCLC). However, how CSCs remodel the immunosuppressive tumor microenvironment (TME) of NSCLC remains largely unclear.</p>Methods<p>Flow cytometry was performed to evaluate the immunomodulatory effects of NSCLC CSCs on T cell differentiation. RNA-sequencing-based metabolic profiling was conducted to identify pivotal metabolic pathways activated in CSCs. Mitochondrial reactive oxygen species (ROS) encapsulated in CSC-derived exosomes were quantified, and the molecular mechanism by which exosomal ROS modulates intracellular nitric oxide (NO) production and FoxP3 post-translational modifications in T cells was further explored. Patient-derived organoids (PDOs) were utilized as a preclinical model to verify the therapeutic potential of glutamine metabolism targeting.</p>Results<p>NSCLC CSCs potently induced tumor immunosuppression by promoting regulatory T (Treg) cell differentiation. Mechanistically, hyperactive glutamine metabolism in CSCs substantially increased mitochondrial ROS generation. Exosomal ROS secreted by CSCs was transferred to T cells, thereby elevating intracellular NO synthesis. Increased NO further triggered S-nitrosylation and deubiquitination of FoxP3, which ultimately stabilized FoxP3 expression and facilitated Treg cell differentiation. In NSCLC PDO models, pharmacological inhibition of glutamine metabolism reversed the immunosuppressive T cell phenotype and efficiently suppressed PDO growth.</p>Conclusion<p>NSCLC CSCs mediate TME immunosuppression via a glutamine metabolism-dependent regulatory axis. Exosomal ROS-initiated FoxP3 post-translational modification is a novel mechanism underlying CSC-driven Treg differentiation. This study reveals an unreported immune evasion pathway in NSCLC and identifies glutamine metabolism as a viable therapeutic target for overcoming tumor immunosuppression.</p> 2026-09-15T04:24:19Z Dataset Dataset 10.3389/fimmu.2026.1961819.s001 https://figshare.com/articles/dataset/Data_Sheet_1_Cancer_stem_cell_programs_S-nitrosylation_and_deubiquitination_of_FoxP3_protein_to_promote_regulatory_T_cell_differentiation_pdf/33770596 CC BY 4.0