Tumor Suppression by Anti-Fibroblast Activation Protein Near-Infrared Photoimmunotherapy Targeting Cancer-Associated...

Area of Science:

• Oncology
• Immunotherapy
• Cancer Biology

Background:

• Cancer-associated fibroblasts (CAFs) promote tumor growth and immune suppression.
• Targeting fibroblast activation protein (FAP) on CAFs has shown limited success in clinical trials.
• Near-infrared photoimmunotherapy (NIR-PIT) offers a selective tumor-targeting approach.

Purpose of the Study:

• To evaluate the therapeutic efficacy of NIR-PIT targeting FAP for CAF depletion in preclinical cancer models.
• To assess the impact of FAP-targeted NIR-PIT on tumor growth, immune cell activation, and metastasis.

Main Methods:

• NIR-PIT targeting FAP and podoplanin was performed in syngeneic lung and spontaneous mammary tumor mouse models.
• Tumor growth, FAP+ cell depletion, and immune cell responses (IFN-gamma) were analyzed.
• Bone marrow chimeras were used to investigate the role of FAP+ stromal and myeloid cells.

Main Results:

• Anti-FAP NIR-PIT effectively depleted FAP+ CAFs and FAP+ myeloid cells, suppressing tumor growth.
• Anti-podoplanin NIR-PIT showed no significant anti-tumor effect.
• Anti-FAP NIR-PIT induced interferon-gamma production by CD8 T and NK cells.
• Lung metastases were reduced in the spontaneous mammary cancer model.

Conclusions:

• Targeting FAP+ cells, including both stromal and myeloid populations, via NIR-PIT is a promising therapeutic strategy.
• This approach effectively suppresses tumor growth and may reduce metastasis.
• NIR-PIT offers a selective method for eliminating immunosuppressive cells within the tumor microenvironment.