Cholesterol Metabolism Modulation Nanoplatform Improves Photo-Immunotherapeutic Effect in Oral Squamous Cell Carcinoma

Impressive results in cancer treatment have been obtained through immunotherapy. However, abnormally high cholesterol metabolism in the tumor microenvironment (TME) leads to poor immunogenicity or even immunosuppression, which dramatically reduces the clinical response of patients with oral squamous cell carcinoma (OSCC) to immunotherapy. In this study, a cholesterol-modulating nanoplatform (PYT NP) is developed to restore the normal immune microenvironment, significantly inhibiting SQLE (an essential gene for cholesterol biosynthesis in tumor cells) by releasing terbinafine, thereby reducing cholesterol in the TME and suppressing tumor cell proliferation. In addition, the nanoplatform is equipped with a second near-infrared (NIR-II) photosensitizer, Y8, which triggers immunogenic cell death of tumor cells, thereby promoting intra-tumor infiltration and immune activation via the production of damage-associated molecular patterns for photoimmunotherapy. PYT NPs show great promise in stimulating strong cholesterol-modulating anticancer immunity combined with photoimmunotherapy, opening up a new avenue for sensitized OSCC immunotherapy.

Automated summary

Impressive results have been achieved in cancer treatment through immunotherapy. However, the abnormally high cholesterol metabolism in the tumor microenvironment (TME) hinders immunotherapy's effectiveness in patients with oral squamous cell carcinoma (OSCC). A cholesterol-modulating nanoplatform (PYT NP) was developed in this study to restore the normal immune microenvironment by reducing cholesterol in the TME, inhibiting tumor cell proliferation, and triggering immunogenic cell death. Equipped with a near-infrared photosensitizer (Y8), the nanoplatform promotes immune activation and intra-tumor infiltration for photoimmunotherapy. PYT NPs show great potential in sensitized OSCC immunotherapy.