Mechanism Study on GZMB Inhibiting Cervical Cancer Metastasis by Regulating CD8+T Cell Pyroptosis and SPP1 Expression
Cervical cancer metastasis severely impacts patient prognosis, with distant metastasis significantly reducing the 5-year survival rate. However, the molecular mechanisms underlying immunotherapy for cervical cancer metastasis remain unclear. This study investigated the role of GZMB in regulating CD8+T cell pyroptosis and cervical cancer metastasis, as well as its association with SPP1.Tissue and blood samples (lung, bone, and subcutaneous) were collected from patients with cervical cancer without metastasis and with distant metastasis. Single-cell RNA sequencing was performed, validated with the TCGA database, and analyzed using the KEGG pathway. Results showed a significant decrease in CD8+T cells and macrophages in metastatic tissues, as well as aberrant expression of pyroptosis-related genes (GZMB, GSDME, and NLRP3). GZMB promotes CD8+T cell pyroptosis by cleaving GSDME and activating the NLRP3 inflammasome; its elevated expression correlates with downregulation of SPP1 in effector T cells. High GZMB expression indicates a favorable prognosis, whereas high SPP1 expression indicates a poor prognosis. GZMB and its upstream genes (JARID2 and ZNF484) may participate in cervical cancer metastasis by regulating SPP1.In summary, GZMB inhibits cervical cancer metastasis by regulating CD8+T cell pyroptosis, and SPP1 can serve as a metastasis biomarker. The GZMB-SPP1 axis provides a new target for cervical cancer immunotherapy, but its direct regulatory relationship and potential for clinical translation require further verification.