To investigate whether modulating autophagy can transform “immune cold” lung tumors into “immune hot” tumors, thereby improving sensitivity to immune checkpoint inhibitors (ICIs), a lung Cancer-on-a-Chip model incorporating NSCLC, mesenchymal stromal cells, endothelial cells, fibroblasts, macrophages, and extracellular matrix (ECM) components will be designed to reproduce the cold tumor microenvironment (TME). Using such a microphysiological platform, the effects of pembrolizumab, novel anticancer drug candidates, platinum and palladium complexes, and resveratrol-conjugated gold nanoparticles will be evaluated. My research will further evaluate LC3-II, p62, GFP-LC3 puncta, and autophagic flux, etc to understand the interference with autophagy. Therefore, the present study seeks to understand how autophagy can reprogram the TME and reactivate antitumor immune responses, hence to improve ICI efficacy. Cytotoxicity, apoptosis, oxidative stress, and ATP production will also be assessed. Nevertheless, in summary, my research is expected to integrate cancer biology, autophagy, immunology, nanotherapeutics, drug screening, and physiological tumor modeling, aiming to identify innovative and translational strategies to overcome immunotherapy resistance in lung cancer subtypes and advance preclinical drug evaluation.