Curcumin Micelles Remodel Tumor Microenvironment and Enhance Vaccine Activity in an Advanced Melanoma Model

摘要: Previously, we have reported a lipid-based Trp2 peptide vaccine for immunotherapy against melanoma. The suppressive immune microenvironment in the tumor is major hurdle an effective therapy. We hypothesized that curcumin (CUR) would remodel to improve activity. Curcumin–polyethylene glycol conjugate (CUR–PEG), amphiphilic CUR-based micelle, was delivered intravenously (i.v.) tumor. Indeed, B16F10 tumor–bearing mice, combination of CUR–PEG and treatment resulted synergistic antitumor effect ( P vivo cytotoxic T-lymphocyte response (41.0 ± 5.0% specific killing) interferon-γ (IFN-γ) production (sevenfold increase). In microenvironment, therapy led significantly downregulated levels immunosuppressive factors, such as decreased numbers myeloid-derived suppressor cells regulatory T (Treg) declined interleukin-6 chemokine ligand 2—in correlation with increased proinflammatory cytokines, including necrosis factor-α IFN-γ well elevation CD8 + T-cell population. results indicated distinct M2 M1 phenotype switch treated tumors. Combining also dramatically signal transducer activator transcription 3 pathway (76% reduction). Thus, conclude agent advanced