Superparamagnetic iron oxide nanoparticle restores gut microbiota homeostasis to enhance lung cancer immunotherapy

Emerging evidence indicates that gut microbiota dysbiosis markedly compromises the efficacy of lung cancer immunotherapy. In our study, superparamagnetic iron oxide nanoparticle assemblies (SPIOCAs) were developed and shown to effectively inhibit lung cancer growth at a dose of 12.5 mg/kg. Pretreatment with broad-spectrum antibiotics aggravates the gut dysbiosis that blunts programmed cell death protein 1 (PD-1) blockade in tumor-bearing mice, whereas SPIOCA administration reconstituted the gut microbiota and thereby resensitized tumors to anti-PD-1 therapy. SPIOCA gavage fortified intestinal barrier integrity-evidenced by elevated ZO-1, ZO-2, Occludin and Claudin-1 expression-and potentiated antitumor immune-cell infiltration, specifically by CD8+ T cells and dendritic cells, into the tumor microenvironment. We therefore preliminarily conclude that SPIOCAs restore gut microbiota homeostasis in lung cancer, thereby enhancing intestinal barrier integrity and converting the tumor immune microenvironment from an immune desert to an immune-inflamed phenotype, ultimately improving lung cancer immunotherapy efficacy.