Mechanisms and related cellular and molecular pathways of liver injury caused by targeted therapy and ICIs, alone or in combination (IMAGE)
Caption
Tyrosine kinase inhibitors (TKIs) are metabolized via the cytochrome P450 pathway, which may be associated with the production of toxic intermediates. These drugs can also induce oxidative stress and activate apoptotic pathways, leading to the activation of immune responses. Immune checkpoint inhibitors (ICIs) deplete Treg cells, inducing a reduction of anti-inflammatory cytokines and proliferation of CD8+ T cells. ATP, adenosine triphosphate; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; CYP450, cytochrome P450; DAMPs, damage-associated molecular patterns; TCR, T cell receptor; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor; GSH, glutathione; HMGB1, high mobility group B1; UGT1A9, uridine diphosphate glucuronosyltransferase 1A9; ROS, reactive oxygen species.
Credit
Yuemin Nan, Xiaoyuan Xu, Jingfeng Liu
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CC BY-NC