Development of tumor microenvironment-modulating nanoparticles for improved anti-tumor efficacy of immunotherapy
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초록
내용
Immune checkpoint blockade therapies (ICT) have revamped the cancer treatment landscape by restoring T cell effector functions. However, cancer cells have evolved to escape from this immune response by changing the tumor microenvironment (TME), which cannot induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection. To address such limitations, we designed TME-modulating nanoparticles (NP@M) consisting of biocompatible polymeric shells and macitentan inside the particles. Macitentan can regulate immune-suppressing TME by inactivating cancer-associated fibroblast. TME remodeling using NP@M allowed the superior antitumor efficacy of ICT. The reduction of tumor volume was maximized in NP@M+ICT combination group. Otherwise, the number of regulatory T cells and the level of TGF-β1 were reduced in tumor site of NP@M+ICT treated group. Our findings suggested that combination therapy with NP@M can be an innovative methodology to elicit CTL-mediated immunological rejection of tumors.