Targeting latency-associated peptide promotes antitumor immunity.

Area of Science:

• Immunology
• Oncology
• Cancer Research

Background:

• Regulatory T cells (Tregs) suppress anti-tumor immune responses, promoting cancer progression.
• The latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on Tregs is a key immunosuppressive target.

Purpose of the Study:

• To evaluate the efficacy of anti-LAP antibody therapy in enhancing anti-tumor immunity.
• To investigate the mechanisms by which anti-LAP antibody affects immune cells and tumor growth.

Main Methods:

• Treatment with anti-LAP antibody in preclinical models of melanoma, colorectal carcinoma, and glioblastoma.
• Analysis of Treg populations, dendritic cell function, TGF-β secretion, and CD8+ T cell activation.
• Characterization of CD103+ CD8 T cells in tumor microenvironment and lymphoid organs.

Main Results:

• Anti-LAP antibody treatment reduced LAP+ Tregs, tolerogenic dendritic cells, and TGF-β secretion.
• Increased infiltration of cytotoxic CD8+ T cells into tumors and activation of CD8+ T cells were observed.
• CD103+ CD8 T cells were identified as a tolerogenic population that promotes tumor growth, and their blockade limited tumorigenesis.

Conclusions:

• Anti-LAP antibody therapy effectively enhances anti-tumor immune responses and reduces tumor growth.
• The therapy targets multiple immunosuppressive pathways, including Treg function and CD103+ CD8 T cell activity.
• Anti-LAP antibody represents a promising strategy for cancer immunotherapy.