Steroid receptor coactivator 3-deficient regulatory T cells eradicate multiple solid tumors in syngeneic mouse models

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Steroid receptor coactivator 3 (SRC-3) is crucial for regulatory T cell (Treg) immunosuppressive function.
• Disrupting SRC-3 in Tregs has previously shown efficacy against triple-negative breast cancer (TNBC) and prostate cancer in preclinical models.
• SRC-3 knockout (KO) Tregs promote infiltration of anti-tumor immune cells like CD8+, CD4+, and NK cells into the tumor microenvironment (TME).

Purpose of the Study:

• To investigate the efficacy of SRC-3-deficient Tregs in eradicating other solid tumors.
• To determine if SRC-3 targeted Treg modulation can establish an anti-tumor immune environment in diverse cancer types.
• To evaluate the potential of SRC-3 targeted Treg modulation as a broad-spectrum immunotherapy platform.

Main Methods:

• Utilized syngeneic mouse models for glioblastoma, melanoma, and lung cancer.
• Generated SRC-3 knockout (KO) regulatory T cells (Tregs).
• Administered SRC-3 KO Tregs to tumor-bearing mice and assessed tumor eradication and immune cell infiltration.

Main Results:

• SRC-3 KO Tregs demonstrated potent anti-tumor effects, eradicating glioblastoma, melanoma, and lung cancer in respective models.
• The treatment generated a robust anti-tumor immune environment.
• No immune-related adverse events (irAEs) were observed, indicating a favorable safety profile.

Conclusions:

• SRC-3 targeted Treg modulation is a promising strategy for inducing potent anti-tumor immunity across multiple cancer types.
• This approach effectively generates an anti-tumor immune microenvironment without inducing irAEs.
• SRC-3 KO Tregs represent a potential safe and effective immunotherapy platform for treatment-refractory cancers.