Natural Killer Cell-Derived Extracellular Vesicles Exhibit Cytotoxicity Against Bulk Tumor Cells and Cancer Stem...

Area of Science:

• Oncology
• Immunotherapy
• Cell Biology

Background:

• Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to limited treatment efficacy and the development of drug resistance.
• Cancer stem cells (CSCs) contribute to TNBC recurrence and treatment failure, highlighting the need for novel therapeutic targets.
• Current therapies for TNBC, including chemotherapy and radiation, have suboptimal outcomes, necessitating innovative treatment strategies.

Purpose of the Study:

• To investigate the therapeutic potential of natural killer cell-derived extracellular vesicles (NK-EVs) against triple-negative breast cancer (TNBC).
• To evaluate the efficacy of NK-EVs in targeting both TNBC cells and cancer stem cells (CSCs).
• To elucidate the mechanisms underlying NK-EVs' cytotoxic effects on TNBC.

Main Methods:

• Utilized clinically relevant models, including patient-derived xenografts, to assess NK-EV efficacy.
• Performed pathway analysis to identify mechanisms of NK-EV-induced cell death.
• Assessed the impact of NK-EVs on the viability and functionality of TNBC CSCs and non-CSCs.

Main Results:

• NK-EVs demonstrated significant cytotoxicity against TNBC cells and CSCs, inducing apoptosis and necrosis.
• NK-EV treatment disrupted the functionality and viability of TNBC CSCs.
• Increased expression of apoptosis markers was observed in both CSCs and non-CSCs following NK-EV treatment.

Conclusions:

• NK-EVs represent a promising cell-free therapeutic strategy for triple-negative breast cancer.
• NK-EVs exhibit potent anti-cancer effects by inducing apoptosis and necrosis and by targeting CSCs.
• These findings support the translational potential of NK-EV-based immunotherapies for aggressive breast cancer subtypes.