Codelivery of triptolide and IFN-γ to boost antitumor immunity for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a specific type of breast cancer that exhibits poor prognosis and complex tumor heterogeneity. The unique immune tumor microenvironment reveals great potential of immunotherapy in TNBC. Triptolide, a potential regulator of immune-related signaling, has shown potent antitumor activity in TNBC. However, the molecular mechanism of triptolide in TNBC is still controversial. This study identified interferon-γ (IFN-γ) as a therapeutical target of triptolide based on the analysis of prognostic biomarkers in TNBC. IFN-γ is an important component of immunotherapy and contributes to antitumor immune activation. Triptolide was found to significantly reverse the IFN-γ-inducible programmed death-ligand 1 (PD-L1) in TNBC. The combined treatment of triptolide and IFN-γ in a hydrogel delivery system remarkably induced the cytotoxic CD8 + T lymphocytes activation, showing a synergistic effect on the potent tumor inhibition.