Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
Cet article décrit les différents points de contrôle immunitaire, présente différentes voies pour inhiber ces points de contrôle, analyse le rôle de différents facteurs dans la réponse thérapeutique et la toxicité des inhibiteurs de point de contrôle immunitaire puis examine les stratégies pour améliorer leur efficacité et réduire leur toxicité
Unprecedented advances have been made in cancer treatment with the use of immune checkpoint blockade (ICB). However, responses are limited to a subset of patients, and immune-related adverse events (irAEs) can be problematic, requiring treatment discontinuation. Iterative insights into factors intrinsic and extrinsic to the host that impact ICB response and toxicity are critically needed. Our understanding of the impact of host-intrinsic factors (such as the host genome, epigenome, and immunity) has evolved substantially over the past decade, with greater insights on these factors and on tumor and immune co-evolution. Additionally, we are beginning to understand the impact of acute and cumulative exposures?both internal and external to the host (i.e., the exposome)?on host physiology and response to treatment. Together these represent the current day hallmarks of response, resistance, and toxicity to ICB. Opportunities built on these hallmarks are duly warranted.
Cell , résumé, 2020