To further investigate the impact of prepared TMTP1-TSRP-EVs on the primary immune checkpoint resistance in PI3K-mutant NSCLC, we co-cultured EVs from different groups with A549 cells and assessed their effects on the PI3K/AKT/mTOR pathway, PD-L1 protein, CD8+ T cells, and tumor cells. Here, PIK3CA is linked to non-small cell lung carcinoma.