Abstract

This study focuses on the immune escape mechanism of lung adenocarcinoma (LUAD), aiming to explore the role of hypoxia and immune-related factor ANGPTL4 in regulating M2 polarization of tumor-associated macrophages (TAMs) and its molecular pathway. The background is that the M2-type polarization of TAMs in the LUAD microenvironment is a key link in promoting tumor progression and immunosuppression, while ANGPTL4, as a factor highly expressed in patients with high hypoxia-immune index, its specific regulatory mechanism remains unclear. It is worth noting that in the field of modern medical laboratory testing, electrochemical sensors have become a cutting-edge technology for real-time and dynamic monitoring of key biomarkers in the tumor microenvironment, such as cytokines, REDOX active substances, and ferroptosis-related metabolites, due to their high sensitivity, rapid response, low cost, and potential for miniaturization. This technology provides a powerful tool for label-free and in situ analysis of macrophage functional status by converting biometric events into quantifiable electrical signals. It is particularly suitable for immediate and multi-parameter detection of secreted proteins such as ANGPTL4 and their downstream effector molecules, and has great prospects for transformation into point-of-care testing (POCT). The TAMs model was constructed by co-culturing THP-1-derived macrophages with LUAD cells (A549/Calu-3), combined with hypoxia treatment, and the expression of ANGPTL4 was regulated through siRNA interference and pcDNA overexpression techniques. The potential mechanisms were screened by transcriptome sequencing, and the effects of ANGPTL4 on TAMs polarization and the NF-κ B-SLC7A11-ferroptosis pathway were verified by Western blot, qRT-PCR, flow cytometry and ELISA. In summary, ANGPTL4 inhibits ferroptosis through the NF-κB-SLC7A11 axis, drives TAMs to polarization towards the M2 type, and thereby promotes the progression of LUAD.