Study on the Molecular Mechanism of Salidroside@T-exo Inducing Breast Cancer Immune Microenvironment Remodeling and Reversing Acquired Resistance to Immunotherapy by Regulating the PI3K/AKT/mTOR Signaling Pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Jun Qian
PROVIDER: PXD070218 | iProX | Mon Nov 03 00:00:00 GMT 2025
REPOSITORIES: iProX
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Project description:Breast cancer (Breast Cancer, BC) patients often face the issue of acquired resistance during PD-1 immunotherapy, which significantly limits the efficacy and durability of treatment. Research indicates that the tumor immune microenvironment is closely linked to the development of resistance. To address this challenge, this study aims to regulate the PI3K/AKT/mTOR signaling pathway by using Salidroside-loaded oligopeptide-modified tumor stem cell-derived exosomes (Salidroside@T-exo), thereby reshaping the immune microenvironment of breast cancer and reversing PD-1 immunotherapy resistance. We modified the oligopeptide TMTP1 onto the surface of tumor stem cell exosomes and introduced Salidroside via electroporation to prepare Salidroside@T-exo. The experiment involved in vitro construction of a MA782/5s-8101 PD-1-resistant cell model, combined with high-throughput sequencing, proteomics, and metabolomics analyses, to investigate the effects of Salidroside@T-exo on tumor cell proliferation, metabolism, and the immune microenvironment. The results demonstrated that Salidroside@T-exo significantly inhibited the activity of the PI3K/AKT/mTOR signaling pathway, enhanced T cell proliferation and tumor cell-killing capacity, reshaped the immune microenvironment, and successfully reversed PD-1 resistance. Our study provides an innovative therapeutic strategy for breast cancer, which may help improve the efficacy of immunotherapy.
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