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

• DOI: 10.3389/fcell.2021.720472
• Publication Date: 2021-12-01T01:22:43Z
• Authors: Qiang Fu; Qian Shen; Jin Tong; Liu Huang; Yi Cheng; Wei Zhong
• Keywords: Tumor-infiltrating lymphocytes; Cancer Immunotherapy; Proinflammatory cytokine

Breast cancer is a leading type of malignant tumor in women; however, the immunotherapy breast still underappreciated. In this study, we demonstrated that necrosis factor receptor 2 (TNFR2) highly expressed both tissue and tumor-infiltrating immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs). We found TNFR2 antagonistic antibody reduced Foxp3 expression proliferation Tregs impaired inhibitory effect on CD4+CD25- effector (Teff) dose-dependent manner. The treatment anti-TNFR2 not only inhibited vitro but also suppressed tumorigenesis murine mammary carcinoma 4T1 vivo. Mice recovered from growth developed 4T1-specific immunity. Furthermore, combination with anti-PD-L1 exhibited augmented antitumor effects than monotherapy. Anti-TNFR2 tended to increase proinflammatory cytokines tissues. conclusion, our study suggests antagonist could potentially offer clinical benefit as single agent or immune checkpoint blockade for immunotherapy.