MiPEP133 enhances anti-tumor immunity in nasopharyngeal carcinoma by activating CD8 + T cells.

BACKGROUND: Activation of the tumor immune microenvironment (TIME) is crucial for controlling nasopharyngeal carcinoma (NPC) progression. This study aims to identify miPEP133 as novel therapeutic targets for NPC treatment. METHODS: RNA-Seq was used to assess miPEP133's effect on NPC cells and T-cell-related signaling pathways. IHC measured miPEP133 protein expression in human NPC tissues. Functional assays evaluated miPEP133's role in anti-tumor immunity. NPC cells were co-cultured with T cells to examine miPEP133's impact on CD8 + T-cell activation, cytotoxic factor secretion, and DC maturation via flow cytometry, ELISA, and a subcutaneous xenograft model. Immunofluorescence (IF), ELISA, and Western blot assessed miPEP133's effect on NPC cell immunogenicity. Finally, electron microscopy, IF, Western blot, and RT-qPCR systematically verified miPEP133's molecular mechanism in NPC cells and its immunomodulatory effects on T cells. RESULTS: This study confirmed that miPEP133 expression in NPC was positively correlated with CD8 + T-cell-mediated anti-tumor immunity and may serve as an independent prognostic factor for survival. High miPEP133 increased CD8 + T-cell infiltration, enhanced secretion of Granzyme B, IFN-γ, and IL-2 from CD8 + T cells, and promoted DC maturation. Moreover, miPEP133 boosted tumor cell antigen presentation via endoplasmic reticulum stress. In a nude mouse xenograft model, miPEP133 significantly inhibited tumor growth, further validating its role in enhancing anti-tumor immunity. Mechanistically, miPEP133 activated type I interferon responses by regulating the STING pathway, subsequently reactivating T-cell immunity via the JAK1/STAT1/STAT4 axis. CONCLUSIONS: MiPEP133 overexpression in NPC cells significantly enhances CD8 + T-cell-mediated immunity, revealing a novel anti-tumor mechanism. These findings demonstrate miPEP133's critical role in shaping the NPC immune microenvironment, highlighting its therapeutic potential.