Countering postoperative immune suppression with a self-assembling dendritic cell nanovaccine

Area of Science:

• Immunology
• Cancer Research
• Biotechnology

Background:

• Postoperative immune suppression impairs T cell responses and increases cancer recurrence risk.
• Transforming growth factor β (TGFβ) causes dendritic cell (DC) dysfunction via lysosomal incompetence, linked to prosaposin (pSAP) loss.
• Surgery-induced immunosuppression poses a significant challenge for effective cancer treatment.

Purpose of the Study:

• To develop a novel vaccine platform, BAIT (boosting antigen-delivering immunovaccine for T cell priming), to counteract postoperative immune suppression.
• To restore DC function by targeting the lysosomal mTOR-pSAP axis.
• To create a personalized immunotherapy strategy for postoperative cancer patients.

Main Methods:

• Designed BAITs using an arginine-enriched peptide backbone for DC recruitment, antigen delivery, and immune activation.
• Co-assembled tumor lysate antigens and CCL20 within BAITs.
• Utilized a functional precision medicine approach, customizing tumor lysates from ferroptosis, necroptosis, or apoptosis.
• Administered BAITs early post-surgery in a murine model.

Main Results:

• BAITs successfully recruited DCs, enhanced antigen internalization, and activated the mTOR pathway to upregulate pSAP.
• BAIT administration reversed TGFβ-induced impairments in DC antigen digestion and MHC-peptide complex formation.
• Apo-BAITs, using apoptotic tumor lysates, reduced tumor burden by 85.5% in a murine postoperative cancer model.

Conclusions:

• BAITs effectively restore DC function by targeting the lysosomal mTOR-pSAP axis, overcoming surgery-induced immune suppression.
• This platform offers a personalized strategy for postoperative cancer vaccination.
• BAITs demonstrate significant potential in reducing cancer recurrence after surgery.