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The complex role of PD-L1 in antitumor immunity: a recent update

Cellular & Molecular Immunology volume 18, pages 2067–2068 (2021)Cite this article

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PD-1, a member of the immunoglobulin gene superfamily, was found to be involved in programmed cell death and subsequently demonstrated to be critical for the negative regulation of T cells. Its ligands PD-L1 (B7-H1) and PD-L2 (B7-DC) interact with PD-1 and negatively regulate T cell-mediated immune responses.1 CD80 also interacts with PD-L1 as a counterreceptor. Moreover, PD-L1 can serve as a receptor to transmit signals to T cells and tumor cells to resist immune-mediated destruction.1 Therefore, PD-L1 can act as both a ligand and a receptor for immunoregulatory functions. This commentary will focus on the roles of various cellular sources of PD-L1 in regulating antitumor immunity.

In addition to tumor cells, activated immune cells, such as T cells, B cells, and natural killer (NK) cells, often express PD-L1.1 PD-L1 is also commonly expressed on myeloid cells, including macrophages, myeloid-derived suppressor cells, and dendritic cells (DCs), in the tumor microenvironment.1 The expression of PD-L1 can be upregulated in both tumor cells and normal cells by many cytokines, especially interferon-γ.1 The contribution of PD-L1-expressing cells to antitumor T cell suppression is critical for stratifying patients for their response to anti-PD-1/PD-L1 immunotherapy and for understanding PD-L1-mediated inhibitory mechanisms in detail.

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Fig. 1: Timeline of some key discoveries and advances related to PD-L1 in antitumor immunity.

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Acknowledgements

X.Y. was supported by the National Natural Science Foundation of China (81971467).

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  1. These authors contributed equally: X Zhang, Y Huang

Authors and Affiliations

  1. Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

    Xiaoqing Zhang, Yue Huang & Xuanming Yang

  2. Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, China

    Xuanming Yang

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  1. Xiaoqing Zhang
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Correspondence to Xuanming Yang.

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Zhang, X., Huang, Y. & Yang, X. The complex role of PD-L1 in antitumor immunity: a recent update. Cell Mol Immunol 18, 2067–2068 (2021). https://doi.org/10.1038/s41423-021-00702-y

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