Galectin-3 suppresses CD8⁺ T cells function via myeloid-derived suppressor cells recruitment in cervical cancer

The tumor immune microenvironment is crucial in tumor development. Galectin-3 (GAL3), a beta-galactoside-binding lectin and tumor secretory protein, is increasingly recognized as a key mediator of immunosuppression in various cancers; however, its role in cervical cancer (CC) immune escape has not been well studied. This study investigates GAL3 regulation of myeloid-derived suppressor cells (MDSCs) through immune infiltration, flow cytometry, cytokine screening, and animal models. Particularly, GAL3 was upregulated in CC samples and was significantly correlated with lymph node metastasis, recurrence, and survival. Correlation analysis showed that GAL3 expression was correlated with the aggregation of MDSCs. Patients with high MDSCs infiltration have a poor prognosis. Mechanistically, GAL3 promoted MDSCs recruitment by activating STAT3/Akt signaling pathway. Additionally, MDSCs inhibited CD8⁺ T cells function by secreting interleukin-6 (IL-6) and C-X-C motif chemokine ligand 2 (CXCL2). Furthermore, GAL3 and MDSCs inhibitors diminished subcutaneous tumor in vivo by reducing MDSCs accumulation and increasing CD8⁺ cells infiltration. This study demonstrates that GAL3 enhances the immunosuppressive function of MDSCs in CC, leading to impaired CD8⁺ T cells function and poor patient prognosis. These findings identify GAL3 and MDSCs as promising targets for therapeutic intervention, providing a basis for novel immunotherapeutic approaches in CC treatment.