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Checkpoint Inhibitors and Hepatotoxicity

Journal

BIOMEDICINES
Volume 9, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9020101

Keywords

checkpoint inhibitors; hepatotoxicity; drug induced liver injury; tumor cells; immunological escape; malignant cells; cytokines

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Uncontrolled immune responses to pathogens or proteins can lead to tissue damage and autoimmune diseases. The immune checkpoint system regulates immune responses, with tumor cells evading immune surveillance by activating checkpoints. Targeting immunological escape of malignant cells is the basis of immune oncology, with immunomodulatory agents enhancing the immune system's response to tumors.
Uncontrolled immune response to a pathogen or any protein can lead to tissue damage and autoimmune diseases, that represent aberrant immune responses of the individual to its own cells and/or proteins. The immune checkpoint system is the regulatory mechanism that controls immune responses. Tumor cells escape the immune surveillance mechanism, avoiding immune detection and elimination by activating these checkpoints and suppressing the anti-tumor response, thus allowing formation of tumors. Antigenic modulation facilitates masking and contributes to the escape of tumor cells. In addition, there are growing cell promoters, like transforming growth factor beta (TGF-beta), contributing to escape mechanisms. Targeting the immunological escape of malignant cells is the basis of immune oncology. Checkpoint inhibitors, cytokines and their antibodies may enhance the immune system's response to tumors. Currently, immunomodulatory agents have been designed, evaluated in clinical trials and have been approved by both European and United States Drug Agencies. The present review is a reflection of the increasingly important role of the checkpoint inhibitors. Our aim is to review the side effects with the emphasis on hepatic adverse reactions of these novel biological drug interventions.

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