Blockade of trans PD-L1 interaction with CD80 augments antitumor immunity

作者：Zhang, Yuankun; Song, Qingxiao; Cas***y, Kaniel; Lee, Michael; Tang, Haidong; Zheng, Moqian; Wang, Bixin; Schones, Dustin E.; Fu, Yang-Xin; Riggs, Arthur D.; Martin, Paul J.; Feng, Ru^*; Zeng, Defu^*

来源：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2023, 120(16): e2205085120.

DOI：10.1073/pnas.2205085120

• PD-L1
• CD80
• PD-L1 interaction with CD80
• CD8+T cells
• tumor immunity

PD-L1 has two receptors: PD-1 and CD80. Previous reports assumed that PD-L1 and CD80 interacted in trans, but recent reports showed that only cis PD-L1/CD80 interactions existed, and prevention of cis PD-L1/CD80 interactions on antigen-presenting cells (APCs) reduced antitumor immunity via augmenting PD-L1/PD-1 and CD80/ CTLA4 interactions between T and APCs. Here, using tumor-bearing mice capable of cis and trans or trans only PD-L1/CD80 interactions, we show that trans PD-L1/CD80 interactions do exist between tumor and T cells, and the effects of trans PD-L1/CD80 interactions require tumor cell expression of MHC-I and T cell expression of CD28. The blockade of PD-L1/CD80 interactions in mice with both cis and trans interactions or with only trans interactions augments antitumor immunity by expanding IFN-& gamma;-producing CD8+ T cells and IFN-& gamma;-dependent NOS2-expressing tumor-associated macrophages. Our studies indicate that although cis and trans PD-L1/CD80 interactions may have opposite effects on antitumor immunity, the net effect of blocking PD-L1/CD80 interactions in vivo augments CD8+ T cell-mediated antitumor immunity.

• 单位
  清华大学; 南方医科大学