Extracellular vesicles in cervical cancer: immune regulation and emerging therapeutic opportunities
Extracellular vesicles in cervical cancer: immune regulation and emerging therapeutic opportunities
Cervical cancer remains a major global health challenge despite advances in HPV vaccination, particularly due to limited access to effective therapies in low- and middle-income countries. Increasing evidence indicates that cervical cancer is not only a localized disease but also involves systemic immune dysregulation, characterized by elevated immunosuppressive cell populations such as myeloid-derived suppressor cells (MDSCs) and low-density neutrophils (LDNs). These cells contribute to impaired anti-tumor immunity and are associated with poor clinical outcomes.
This thesis of Jordy Larco Lasso demonstrates that LDNs are expanded in cervical cancer patients and exhibit increased STAT3 activation, contributing to T-cell suppression. It further identifies extracellular vesicles (EVs) as key mediators of systemic communication between tumor cells and the immune system. Tumor-derived EVs were shown to modulate monocyte function, promoting immunoregulatory phenotypes and indirectly suppressing T-cell proliferation.
In addition to their role in disease progression, EVs were explored as therapeutic tools. Macrophage-derived EVs, particularly from M1-like cells, demonstrated anti-tumor effects and were successfully engineered to deliver STAT3-targeting siRNA, reducing tumor cell proliferation.
Overall, this work highlights the dual role of EVs in cervical cancer, contributing to immune evasion while also offering promising avenues for therapeutic intervention.