Tailoring Tumor Cell Golgi Apparatus‐Targeting Self‐Assembled Peptide for Effective Immunotherapy via Reshaping MIF‐Mediated Immunosuppressive Network

Abstract The immunosuppressive network formed by the enhanced crosstalk between tumor cells and various types of immune cells may ultimately lead to the formation of tumor immunosuppressive microenvironment (TIME). The Golgi apparatus (GA) of tumor cells is a key organelle in the formation of a tumor immunosuppressive network. However, there are no studies to show whether interfering with the GA of tumor cells can reshape the immunosuppressive network to enhance the effectiveness of immunotherapy. Therefore, the tumor cell GA‐targeting self‐assembled peptide (NF‐1) is tailored, and confirmed that NF‐1 treatment can achieve an effective immunotherapy and found that tumor cell‐derived GA‐dependent migration inhibitory factor (MIF) mediates the formation of immunosuppressive network in breast cancer (BRCA) through multi‐omics analysis, in vivo, and in vitro experiments. NF‐1 treatment‐induced MIF reduction can reshape the immunosuppressive network and convert a “cold” tumor into a “hot” tumor, thus enabling immunotherapy in BRCA and enhancing the ICB efficacy in colon adenocarcinoma (COAD). This study presents a general strategy for interfering with tumor GA for effective immunotherapy in BRCA, COAD, and other cancers characterized by a “cold” immune microenvironment.