Development\nand Evaluation of Indole-Based Phospholipase\nD Inhibitors for Lung Cancer Immunotherapy

This study explored novel immunomodulatory approaches\nfor cancer\ntreatment, with a specific focus on lung cancer, the leading cause\nof cancer-related deaths worldwide. We synthesized indole-based phospholipase\nD (PLD) inhibitors with various substituents to improve anticancer\nefficacy. Through structure–activity relationship studies,\nthe key compound was identified that significantly inhibiting PLD,\nsuppressing cell growth, viability, and migration <i>in vitro,</i> while inducing apoptosis of lung cancer cells. <i>In silico</i> docking studies confirmed its binding to the PLD1 active site, highlighting\nthe role of specific residues in inhibiting PLD1 activity. The inhibitor\nmodulated oncogenic pathways and immune evasion in lung cancer cells,\nshowing potential for immunotherapy. <i>In vivo</i> experiments\nin a mouse model showed tumor reduction and immune response alteration.\nCombining these inhibitors with gemcitabine, an anticancer drug, synergistically\nenhanced inhibition of lung cancer cell apoptosis and proliferation.\nThis research offers new insights into PLD inhibitor as potential\ncancer therapeutics.