2. Academic Validation
  3. Myeloid-derived suppressor cells regulate the immunosuppressive functions of PD-1-PD-L1+ Bregs through PD-L1/PI3K/AKT/NF-κB axis in breast cancer

Myeloid-derived suppressor cells regulate the immunosuppressive functions of PD-1-PD-L1+ Bregs through PD-L1/PI3K/AKT/NF-κB axis in breast cancer

  • Cell Death Dis. 2021 May 9;12(5):465. doi: 10.1038/s41419-021-03745-1.
Min Liu  # 1,  Feng Wei  # 1,  Jian Wang  # 1,  Wenwen Yu 1,  Meng Shen 1,  Ting Liu 1,  Dong Zhang 1,  Yang Wang 1,  Xiubao Ren 2,  Qian Sun 3
Affiliations

Affiliations

  • 1 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
  • 2 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China. renxiubao@tjmuch.com.
  • 3 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China. sunqian923@126.com.
  • # Contributed equally.
PMID: 33967272 DOI: 10.1038/s41419-021-03745-1
Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells that are closely related to tumor immune escape, but the mechanism by which MDSCs regulate B cells has not been elucidated. Our previous studies revealed that breast cancer-derived MDSCs could induce a group of PD-1-PD-L1+ Bregs with immunosuppressive functions. Here, we reported that blocking PD-1/PD-L1 interaction between MDSCs and B cells could reverse the immunosuppressive functions of PD-1-PD-L1+ Bregs. The activation of PI3K/Akt/NF-κB signaling pathway is essential for PD-1-PD-L1+ Bregs to exert immunosuppressive effects. MDSCs activated the PI3K/Akt/NF-κB pathway in B cells via the PD-1/PD-L1 axis. Furthermore, inhibition of PD-1/PD-L1 or PI3K/Akt signaling suppressed both tumor growth and the immunosuppressive functions of PD-1-PD-L1+ Bregs. Dual suppression of PD-1/PD-L1 and PI3K/Akt exerted better antitumor effect. Finally, MDSCs and PD-1-PD-L1+ Bregs were colocalized in breast Cancer tissues and PD-1-PD-L1+ Bregs were positively correlated with poor prognosis. Thus, MDSC-educated PD-1-PD-L1+ Bregs and their regulatory mechanisms could contribute to the immunosuppressive tumor microenvironment. Our study proposes a novel mechanism for MDSC-mediated regulation of B cell immunity, which might shed new light on tumor immunotherapy.

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