Engineered Bacteria-Nanoparticle Conjugate Reprograms Immunosuppressive Niche via Dendritic Cell-Centric...

Area of Science:

• Immunology
• Biotechnology
• Cancer Research

Background:

• The immunosuppressive tumor microenvironment (TME) hinders T cell activation and immunotherapy efficacy.
• Dendritic cells (DCs) are crucial for adaptive immunity but are often impaired within the TME.
• Innate immunity plays a vital role in supporting T cell activity and immunological memory.

Purpose of the Study:

• To develop a novel platform, M-CHNP/D, to overcome TME-induced immunosuppression.
• To enhance both innate and adaptive immune responses for improved cancer immunotherapy.

Main Methods:

• Engineered a bacteria-nanoparticle hybrid (M-CHNP/D) using *Escherichia coli* and acid-responsive nanoparticles encapsulating a PD-1 blocking peptide.
• Utilized bacterial motility for deep tumor penetration and neutralization of the acidic TME.
• Assessed M-CHNP/D's effects on DC recruitment, antigen presentation, innate immune cell populations, and tumor growth in combination with radiotherapy.

Main Results:

• M-CHNP/D achieved deep tumor penetration and neutralized the acidic TME.
• Induced CCL3 upregulation, enhancing DC recruitment, redistribution, and antigen-presenting capacity.
• Increased innate immune cell populations and promoted antitumor functional reprogramming.
• M-CHNP/D combined with radiotherapy significantly inhibited tumor growth and recurrence.

Conclusions:

• M-CHNP/D effectively modulates the tumor immune microenvironment by enhancing both innate and adaptive immunity.
• This hybrid platform shows significant potential as a strategy to improve cancer immunotherapy outcomes.
• M-CHNP/D offers a promising approach to overcome immunotherapy resistance.