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.