An ultrasmall core–shell silica nanoparticle improves antitumour immunity and survival by remodelling suppressive melanoma microenvironments

Despite the considerable success of clinically approved immune-based therapies for treating advanced melanoma, a significant fraction of patients are not responsive owing to mechanisms engaged by the tumour to evade the immune system. Here we report the surprising finding that a clinically validated and tunable self-therapeutic ultrasmall silica nanoparticle prolongs survival in a highly resistant melanoma model in combination with interleukin-6 and PD-L1 inhibition through activation of the stimulator of interferon genes/interleukin-6/PD-L1 axis and reprogramming of the tumour microenvironment towards a pro-inflammatory phenotype. In a murine model, induction of significant cytotoxic and antitumour inflammatory responses leads to differential activation of immune cell populations in a CD8-dependent manner via type I/II interferon pathways after systemic particle injection. Importantly, these immunostimulatory responses accompany significant reductions in cell populations and receptors driving suppressive activities. Mechanistic insights highlight the potential clinical utility of this platform to maximize antitumour immunity and efficacy by subverting suppressive components in the tumour microenvironment.