Notably, it remodeled the tumor immune microenvironment by promoting CD8+ T cell infiltration, enhancing the secretion of IFN-γ and TNF-α, and reducing the populations of regulatory T cells and myeloid-derived suppressor cells.<h4>Conclusions</h4>Mn<sub>3</sub>O<sub>4</sub>/QD@LM confirms the synergistic role of multi-enzyme activities and STING pathway activation in potentiating sonodynamic immunotherapy, and provides an innovative strategy to overcome TME-mediated therapy resistance. The gene discussed is IFNG; the disease is neoplasm.