Reprogramming the Immunosuppressive Microenvironment in Triple-Negative Breast Cancer via FAP-Targeted Nanoprobes for...

Area of Science:

• Oncology
• Nanomedicine
• Immunotherapy

Background:

• Triple-negative breast cancer (TNBC) is aggressive, metastatic, and lacks targeted therapies.
• The tumor microenvironment, influenced by cancer-associated fibroblasts (CAFs), promotes immunotherapy resistance.
• Fibroblast activation protein (FAP) plays a key role in FAP-mediated extracellular matrix (ECM) remodeling.

Purpose of the Study:

• To develop FAP-targeted nanoprobes for precision theranostics in TNBC.
• To investigate a tripartite therapeutic approach to overcome the immunosuppressive tumor microenvironment.
• To evaluate the efficacy of nanoprobes combined with immunotherapy.

Main Methods:

• Development of FAP-targeted nanoprobes (FAP-IR1061) with NIR-II fluorescence, MR, and PA imaging.
• Incorporation of NIR-II photothermal conversion for therapeutic applications.
• Combination therapy with anti-PD-1 (αPD-1) treatment.

Main Results:

• Selective ablation of CAFs and ECM dismantling.
• Induction of immunogenic cell death and repolarization of tumor-associated neutrophils.
• Over 80% suppression of primary and distant tumors when combined with αPD-1 therapy.
• Enhanced infiltration of cytotoxic T lymphocytes.
• Establishment of long-term antitumor immune memory.

Conclusions:

• FAP-targeted nanoprobes offer a promising theranostic strategy for TNBC.
• This approach effectively overcomes the immunosuppressive tumor microenvironment.
• Combination therapy enhances antitumor immunity and prevents tumor recurrence.