Immune checkpoint inhibitors: a narrative review of considerations for the anaesthesiologist

Abstract

Immunotherapy has revolutionised the treatment of oncologic malignancies. Immune checkpoint inhibitors represent a new class of immunotherapy drugs. Although these drugs show promise, they are associated with immune-related adverse reactions. An increasing number of patients who undergo surgery will have had treatment with immune checkpoint inhibitors. In this narrative review article, we discuss their mechanism of action, therapeutic effects, pertinent toxicities, and address specific perioperative considerations for patients treated with immune checkpoint inhibitors.

Keywords: adverse events; anaesthesia; cancer; complications; immune checkpoint inhibitors; immunotherapy; perioperative management; side effects.

Fig 1

Signalling cascade from the interactions of tumour cells and antigen-presenting cells with naive T cells. Two signals are required for T-cell activation and proliferation. The first signal comes from T-cell receptor binding to an antigen presented on a major histocompatibility complex on the surface of a tumour cell/antigen-presenting cell. Without a costimulatory receptor, T cells remain in a quiescent state. The second signal occurs with the binding of CD28 on T cells and B7 proteins on tumour/antigen-presenting cells. These two signals initiate T-cell activation and proliferation. APC, antigen-presenting cells; MHC, major histocompatibility complex; TCR, T-cell receptor. From ‘The future of immunotherapy’, P. Sharma and J. Allison, Science, 2015; 348: 56–61 Reprinted with permission.

Fig 2

Ligand–receptor interactions between tumour cells and activated T cells and targets for anti-PD-1 and anti-CTLA-4 therapy. (a) The interaction of the CTLA-4 receptor on T cells with the CD-80 ligand (B-7 homologue) on an antigen-presenting cells promotes tumour escape. The binding of an anti-CTLA-4 antibody promotes T-cell activation and elimination of tumour cells. (b) The interaction of PD-1 receptor on T cells with PD-L1 ligand on tumour cells promotes T-cell anergy and tumour escape. In the presence of an anti-PD-1 or anti-PD-L1 antibody, T cells become activated and initiate tumour cell death. CTL-4, T-lymphocyte-associated antigen 4; PD-1, programmed cell death 1; APC, antigen-presenting cells; MHC, major histocompatibility complex; TCR, T-cell receptor. From ‘CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition’, E. Buchbinder and A. Desai, American Journal of Clinical Oncology, 2016; 39: 98–106. Reprinted with permission.