Advanced nanomaterials for enhanced immunotherapy via metabolic regulation

The main goal of immunotherapy is to turn "cold" (non-inflamed) tumors into "hot" (inflamed) tumors, hence enhancing the response and cytotoxicity of tumor-specific T cells. In the tumor microenvironment (TME), metabolic reprogramming happens to both tumor and immune cells that will depress the cytotoxicity of T cells and other immune cells, thereby hampering the effectiveness of immunotherapy. This review focuses on the interplay between cancer cells and immune cells within the TME and the role of metabolic reprogramming in the context. We discuss the utilization of nanomaterials as a promising approach to modulate metabolic pathways and enhance immunotherapy outcomes. Specifically, we categorize these nanomaterials based on the metabolites involved in the metabolic regulation. Despite the potential of nanomaterial-based approaches, several challenges persist in the implementation for immune metabolic therapy. We address these challenges and provide insights into the future prospects of designing advanced nanomaterials to overcome these limitations and optimize immunotherapy by targeting metabolic pathways. By understanding and manipulating the metabolic dynamics of cancer and immune cells, it is possible to create a more favorable TME that promotes the activation and cytotoxicity of tumor-specific T cells, ultimately improving the efficacy of immunotherapy.