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Shojaie L, Ali M, Iorga A, et al. Mechanisms of immune checkpoint inhibitor-mediated liver injury. Acta Pharm Sin B. 2021;11(12):3727-3739doi: 10.1016/j.apsb.2021.10.003.
Shojaie, L., Ali, M., Iorga, A., & Dara, L. (2021). Mechanisms of immune checkpoint inhibitor-mediated liver injury. Acta pharmaceutica Sinica. B, 11(12), 3727-3739. https://doi.org/10.1016/j.apsb.2021.10.003
Shojaie, Layla, et al. "Mechanisms of immune checkpoint inhibitor-mediated liver injury." Acta pharmaceutica Sinica. B vol. 11,12 (2021): 3727-3739. doi: https://doi.org/10.1016/j.apsb.2021.10.003
Shojaie L, Ali M, Iorga A, Dara L. Mechanisms of immune checkpoint inhibitor-mediated liver injury. Acta Pharm Sin B. 2021 Dec;11(12):3727-3739. doi: 10.1016/j.apsb.2021.10.003. Epub 2021 Oct 16. PMID: 35024302; PMCID: PMC8727893.
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Acta Pharm Sin B. 2021 Dec;11(12):3727-3739. doi: 10.1016/j.apsb.2021.10.003. Epub 2021 Oct 16.

Mechanisms of immune checkpoint inhibitor-mediated liver injury.

Acta pharmaceutica Sinica. B

Layla Shojaie, Myra Ali, Andrea Iorga, Lily Dara

Affiliations

  1. Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  2. Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  3. Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  4. U.S. Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20993, USA.
  5. UMBC Center for Accelerated Real Time Analytics, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.

PMID: 35024302 PMCID: PMC8727893 DOI: 10.1016/j.apsb.2021.10.003

Abstract

The immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1/ligand-1 (PD-1/PD-L1) are vital contributors to immune regulation and tolerance. Recently immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, they come with the cost of immune related adverse events involving multiple organs such as the liver. Due to its constant exposure to foreign antigens, the liver has evolved a high capacity for immune tolerance, therefore, blockade of the immune checkpoints can result in aberrant immune activation affecting the liver in up to 20% of patients depending on the agent(s) used and underlying factors. This type of hepatotoxicity is termed immune mediated liver injury from checkpoint inhibitors (ILICI) and is more common when CTLA4 and PD-1/PD-L1 are used in combination. The underlying mechanisms of this unique type of hepatotoxicity are not fully understood; however, the contribution of CD8

© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Keywords: Apoptosis; CTLA-4; Cell death; DILI; Hepatocyte; Hepatotoxicity; Immunotherapy; Necrosis; PD-1; PD-L1

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