Translational Selenium Nanoparticles Promotes Clinical Non-small-cell Lung Cancer Chemotherapy via Activating Selenoprotein-driven Immune Manipulation.

Summary

This translational study links selenium deficiency to immune dysfunction in advanced NSCLC, scales GMP production of selenium nanoparticles (SeNPs) to 500 L, and demonstrates that SeNPs activate GPX–mTOR signaling to expand NK cells and boost cytotoxicity. In an investigator-initiated clinical combination with bevacizumab/cisplatin/pemetrexed, SeNPs achieved an 83.3% objective response and 100% disease control, suggesting a selenoprotein-driven immunometabolic augment of chemo-immunotherapy.

Key Findings

• GMP-level 500-L production of selenium nanoparticles was achieved for clinical translation.
• SeNPs activated GPX–mTOR signaling, expanding NK cells and enhancing cytotoxicity against tumor cells.
• In an investigator-initiated clinical combination regimen (bevacizumab/cisplatin/pemetrexed), SeNPs yielded ORR 83.3% and DCR 100%.

Clinical Implications

If validated in randomized trials, SeNP supplementation could be integrated with first-line chemo-immunotherapy to enhance NK-driven antitumor responses in advanced NSCLC; monitoring selenium status may inform patient selection.

Limitations

• Non-randomized investigator-initiated clinical study with unspecified sample size limits causal inference
• Long-term safety, durability of response, and generalizability remain to be established

Future Directions

Conduct multicenter randomized controlled trials to confirm efficacy and safety; define biomarkers (selenium status, selenoprotein/GPX activity, NK functional readouts) for patient selection; evaluate combinations with checkpoint inhibitors.