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Comment
. 2021 Oct 15;81(20):5141-5143.
doi: 10.1158/0008-5472.CAN-21-2926.

Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer

Michael R Pitter  1   2   3 , Weiping Zou  4   2   3
Affiliations
Comment

Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer

Michael R Pitter et al. Cancer Res. .

Abstract

Immune checkpoint blockade involves the targeted antagonism of immunosuppressive interactions between antigen-presenting cells and/or tumor cells and effector T cells. Blockade of B7-H1, also known as programmed death-ligand 1 (PD-L1), prevents the ligation of inhibitory PD-L1 molecules to programmed cell death receptor 1 (PD-1) on T cells, engendering a potentiated response of tumor-specific T cells against tumor cells. In a Cancer Research article, Hirano and colleagues showed that T-cell-mediated tumor immunity becomes impaired when tumor cells interact with T cells via PD-L1 in the mouse tumor microenvironment. They showed that targeting PD-L1 or PD-1 with mAbs increased tumor cell lysis by T cells and suggested that tumor PD-L1 forms a "shield" preventing tumor cell lysis. Alongside other original mouse and human studies, this work generated scientific rationales for a new generation of cancer treatment focused on targeting the inhibitory PD-1/PD-L1 signaling pathway in the tumor microenvironment.See related article by Hirano and colleagues, Cancer Res 2005;65: 1089-96.

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Figures

Figure 1.
Figure 1.
Targeting PD-L1 in cancer. Treatment with PD-L1-blockade therapy reduces PD-L1 expressing cell-mediated T-cell inhibition. Interactions between T-cell PD-1 and PD-L1 on tumor cells or dendritic cells promotes immunosuppression and inhibits antitumor immunity. Antibody-mediated targeting of PD-L1 blocks its ligation to PD-1 to increase activity of tumor-specific T cells against tumor cells.
See this image and copyright information in PMC

Comment on

References

    1. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 1999;5: 1365–9. - PubMed
    1. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192:1027–34. - PMC - PubMed
    1. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002;8:793–800. - PubMed
    1. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003;9: 562–7. - PubMed
    1. Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005;65:1089–96. - PubMed

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