Abstract：Objective: To investigate the correlation and regulatory mechanism between SOX2 and SIRT1 and the cellular immunity level of non-small cell lung cancer patients. Methods: 100 patients with stage III-IV non-small cell lung cancer were included in the study. The spatial heterogeneity of SOX2 expression in tumor tissue was analyzed by immunohistochemistry, and the regulatory effects of SOX2 on immunosuppressive factors, metabolites, and T cell depletion were evaluated using mass spectrometry, flow cytometry, and Luminex multiplex detection omics techniques. Results: The proportion of SOX2 positive cells in the central region of lung squamous cell carcinoma was 82.3%±6.7%, with an H-score of 246±18, significantly higher than that in the peripheral region (41.2%±9.1, P=0.003). The concentration of interleukin-10 in the SOX2 high expression group (34.6±8.5 pg/mL) increased by 2.81 times compared to the control group, and the increase in serum SOX2 concentration led to an increase in the proportion of regulatory T cells from 5.2%±4.1% to 9.4%±0.4% (P<0.05). Conclusion: SOX2 promotes the formation of an immunosuppressive microenvironment by driving metabolic immune imbalance, while SIRT1 suppresses T cell function through epigenetic regulation. The two synergistically mediate immune escape in non-small cell lung cancer, providing a new strategy for targeted intervention.
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2025, Vol. 31 
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