Immune-mediated Adverse Events and Immune Checkpoint Blockade
General Considerations
Immune-mediated Adverse Events and
Immune Checkpoint Blockade
The spectra of Immune-mediated adverse events (imAEs) associated with blockade of immune checkpoints falls in line with the phenotypes observed as a result of mutations in the genes encoding CTLA-4 and PD-1 and has considerable overlap across the various ICIs.1
irAEs may result from some combination of autoreactive T cells, autoantibodies, and/or proinflammatory cytokines (eg, interleukin-17).
One potential mechanism is T-cell activity directed at antigens present in both tumor cells and healthy tissue. – Inflammation in otherwise normal tissues could result from elevated levels of inflammatory cytokines as a downstream effect of T-cell activation
Additionally, direct binding of immune checkpoint antibodies to targets expressed in normal tissues (eg, CTLA expression in the pituitary) could lead to complement-mediated inflammation.
Finally, immunotherapy might increase the levels of preexisting autoreactive antibodies.
irAEs: Immune-Related Adverse Events; ICI: Immune checkpoint inhibitor; imAEs: Immune-mediated adverse event; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4
Reference:
- NCCN (National Comprehensive Cancer Network) V.1.2023. Accessed at: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Last accessed: 5-2023
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