Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in...

Area of Science:

• Immunology
• Oncology
• Cancer Research

Background:

• Breast cancer immunotherapy remains underutilized despite its potential.
• Tumor necrosis factor receptor 2 (TNFR2) is highly expressed in breast tumors and on immunosuppressive regulatory T cells (Tregs).

Purpose of the Study:

• To investigate the therapeutic potential of targeting TNFR2 in breast cancer.
• To evaluate the effects of TNFR2 antagonism on regulatory T cells and tumor growth.

Main Methods:

• Treatment with a TNFR2 antagonistic antibody in vitro and in vivo.
• Analysis of regulatory T cell (Treg) Foxp3 expression and proliferation.
• Assessment of effector T cell (Teff) function and tumor cell proliferation.
• Combination therapy with anti-PD-L1 antibody.

Main Results:

• Anti-TNFR2 antibody reduced Treg proliferation and Foxp3 expression, restoring Teff cell function.
• Inhibition of breast tumor cell proliferation in vitro and suppressed tumor growth in vivo.
• Combination therapy with anti-PD-L1 demonstrated augmented antitumor effects.
• Treatment increased proinflammatory cytokines and induced tumor-specific immunity in recovered mice.

Conclusions:

• TNFR2 antagonism is a promising strategy for breast cancer immunotherapy.
• Anti-TNFR2 antibody can overcome tumor-induced immunosuppression by targeting Tregs.
• This approach offers potential as a monotherapy or in combination with immune checkpoint inhibitors.