Fig. 1: Schematic illustration of engineering radioimmunostimulant nanomedicine synergizing with PD-L1 blockade for postsurgical cancer immunotherapy.
Surgical resection (SR) creates an immunosuppressive milieu characterized by hypoxia and high-influx of myeloid cells. The radioimmunostimulant HMnO2-based nanoplatform (IPI549@HMP) involved in this strategy enables hypoxia-relieved radiotherapy and pH-triggered release of IPI549 capable of targeting myeloid cells, which subsequently remodels immunosuppressive postresection TME into an immunostimulatory phenotype and heightens susceptibility to anti-PD-L1 therapy. IPI549@HMP-augmented radioimmunotherapy in combination with anti-PD-L1 leads to significant inhibition of locally residual and distant tumors, and elicits strong immune memory effect to completely resist tumor rechallenge. ICD, immunogenic cell death; M1, M1-like macrophage; M2, M2-like macrophage; MDSC, myeloid-derived suppressor cell; DC, dendritic cell; CTL, cytotoxic T lymphocyte.
