Cancer immunotherapy and the management of side effects

Abstract

The use of cancer immunotherapies such as immune checkpoint inhibitors (ICIs) has been a paradigm shift in harnessing the immune system to act against cancer cells, and transformed the treatment of several solid and haematological malignancies. Cancer immunotherapies have a unique toxicity profile dependent on their mechanism of action, related to upregulation of immune activity. These can be severe and lead to life-threatening organ toxicity, and therefore identification of at-risk patient groups, early detection and prompt initiation of steroids and other immune-modulating agents is imperative. Acute presentations with toxicity related to these agents comprise a significant proportion of primary and secondary care presentations related to treatment toxicity in oncology. This article will focus on the diagnosis and management of common toxicities associated with immune checkpoint inhibitors, the most commonly utilised cancer immunotherapies.

Keywords: cancer; cancer immunotherapy; immune checkpoint inhibitors; malignancy; toxicity.

Fig 1

Immune checkpoint inhibitors in tumour immunology: mechanism of action. (a) Anti-CTLA-4 antibodies such as ipilimumab block the interaction between CTLA-4 on T-cells and B7 on dendritic cells and other antigen presenting cells, leading to up-regulation of immune activity. (b) PD-1 is expressed on activated T cells; its interaction with PD-L1 expressed by cancer cells causes a reduction in T-cell activity. Blockage of this interaction by an anti-PD-1 or anti-PD-L1 checkpoint inhibitor leads to up-regulation of T-cell activity that can have an anti-cancer effect.