Functional characterization of Foxp3-specific spontaneous immune responses

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are linked to poor cancer prognosis.
• The transcription factor forkhead box P3 (Foxp3) is a key marker for Tregs.

Purpose of the Study:

• To identify and characterize spontaneous cytotoxic immune responses against Foxp3-expressing cells.
• To explore the therapeutic potential of Foxp3-specific cytotoxic T cells in cancer.

Main Methods:

• Analysis of peripheral blood from healthy volunteers and cancer patients.
• Identification of HLA-A2-restricted peptide epitopes derived from Foxp3.
• Characterization of Foxp3-reactive T cells as cytotoxic CD8+ T cells.
• Assessment of T cell recognition of dendritic cells and Tregs.

Main Results:

• Spontaneous cytotoxic immune responses targeting a Foxp3-derived peptide were identified.
• Foxp3-specific cytotoxic T cells recognized and killed Tregs and malignant T cells from Cutaneous T-cell lymphomas (CTCL).
• These T cells recognized dendritic cells incubated with recombinant Foxp3 protein.

Conclusions:

• Foxp3-specific cytotoxic T cells represent a 'suppressor of the suppressors' mechanism.
• Inducing Foxp3-specific cytotoxic T-cell responses is a promising strategy for cancer immunotherapy.