This study reports the development of a novel gene-engineered exosome, PD1-Imi Exo, which combines the PD1 gene with an immune adjuvant, imiquimod, to enhance cancer immunotherapy. The PD1 gene is engineered into HEK 293T cells to produce exosomes that target and bind to cancer cells and dendritic cells (DCs) through the PD1/PDL1 pathway. Imiquimod, a toll-like receptor (TLR) agonist, is then encapsulated into these exosomes to promote DC maturation and restore CD8+ T cell function. The results show that PD1-Imi Exo effectively targets cancer cells and DCs, enhances the maturation of DCs, and improves the killing ability of CD8+ T cells in both melanoma and breast cancer mouse models. This approach demonstrates a promising strategy to reverse T cell exhaustion and improve the efficacy of PD1/PDL1 immunotherapy, potentially preventing tumor recurrence or metastasis.This study reports the development of a novel gene-engineered exosome, PD1-Imi Exo, which combines the PD1 gene with an immune adjuvant, imiquimod, to enhance cancer immunotherapy. The PD1 gene is engineered into HEK 293T cells to produce exosomes that target and bind to cancer cells and dendritic cells (DCs) through the PD1/PDL1 pathway. Imiquimod, a toll-like receptor (TLR) agonist, is then encapsulated into these exosomes to promote DC maturation and restore CD8+ T cell function. The results show that PD1-Imi Exo effectively targets cancer cells and DCs, enhances the maturation of DCs, and improves the killing ability of CD8+ T cells in both melanoma and breast cancer mouse models. This approach demonstrates a promising strategy to reverse T cell exhaustion and improve the efficacy of PD1/PDL1 immunotherapy, potentially preventing tumor recurrence or metastasis.