Regulating tumor cholesterol microenvironment to enhance photoimmunotherapy in oral squamous cell carcinoma

Immunotherapy has drawn much attention in combatting tumors, but the immuno-suppress induced by the high cholesterol concentration in the tumor microenvironment (TME) dramatically hinders the therapeutic effect. Herein, to alter the local immune microenvironment further to promote the effectiveness of tumor immunotherapy, we conduct a cholesterol-regulate nanoplatform (CPSA NPs) that is composed of simvastatin (SIM) packaged chlorin e6-polyethylene glycol (Ce6-PEG) and a targeting-antibody (anti-LDLR) modified on the surface. SIM, as the HMG-CoA reductase (HMGCR) inhibitor, can significantly reduce cholesterol in TME, and unlock the suppression of CD8+ T cells. Ce6-induced PDT&PTT can evoke immunogenic cell death, releasing the tumor-associated antigens (TAAs) during laser irradiation, promoting the anti-tumor immune response, and offering the system anti-tumor immune memory. Both in vitro and in vivo experiments demonstrate that the CPSA NPs have effective tumor cell toxicity, cholesterol regulation effect, and immunity system evoking ability, which brings a new strategy toward immunosuppression from TME, and paves a new way for adjuvant immunotherapy.